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Zhang Q, Niu Y, Li Y, Xia C, Chen Z, Chen Y, Feng H. Meningeal lymphatic drainage: novel insights into central nervous system disease. Signal Transduct Target Ther 2025; 10:142. [PMID: 40320416 PMCID: PMC12050339 DOI: 10.1038/s41392-025-02177-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 12/04/2024] [Accepted: 02/06/2025] [Indexed: 05/08/2025] Open
Abstract
In recent years, increasing evidence has suggested that meningeal lymphatic drainage plays a significant role in central nervous system (CNS) diseases. Studies have indicated that CNS diseases and conditions associated with meningeal lymphatic drainage dysfunction include neurodegenerative diseases, stroke, infections, traumatic brain injury, tumors, functional cranial disorders, and hydrocephalus. However, the understanding of the regulatory and damage mechanisms of meningeal lymphatics under physiological and pathological conditions is currently limited. Given the importance of a profound understanding of the interplay between meningeal lymphatic drainage and CNS diseases, this review covers seven key aspects: the development and structure of meningeal lymphatic vessels, methods for observing meningeal lymphatics, the function of meningeal lymphatics, the molecular mechanisms of meningeal lymphatic injury, the relationships between meningeal lymphatic vessels and CNS diseases, potential regulatory mechanisms of meningeal lymphatics, and conclusions and outstanding questions. We will explore the relationship between the development, structure, and function of meningeal lymphatics, review current methods for observing meningeal lymphatic vessels in both animal models and humans, and identify unresolved key points in meningeal lymphatic research. The aim of this review is to provide new directions for future research and therapeutic strategies targeting meningeal lymphatics by critically analyzing recent advancements in the field, identifying gaps in current knowledge, and proposing innovative approaches to address these gaps.
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Affiliation(s)
- Qiang Zhang
- Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Department of Neurosurgery, The 961st Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Qiqihar Medical University, Qiqihar, 161000, Heilongjiang, China
- Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
| | - Yin Niu
- Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
| | - Yingpei Li
- Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
| | - Chenyang Xia
- Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
| | - Zhi Chen
- Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
- Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
- Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
| | - Yujie Chen
- Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
- Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
- Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
| | - Hua Feng
- Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Key Laboratory of Intelligent Diagnosis, Treatment and Rehabilitation of Central Nervous System Injuries, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
- Chongqing Clinical Research Center for Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
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Chu XL, Zhao XX, Liu SY, Li YJ, Ding N, Liu MQ, Li QW, Li Q. Research progress in different physical therapies for treating peripheral nerve injuries. Front Neurol 2025; 16:1508604. [PMID: 40260135 PMCID: PMC12009707 DOI: 10.3389/fneur.2025.1508604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 02/28/2025] [Indexed: 04/23/2025] Open
Abstract
Physical therapy is gaining recognition as an effective therapeutic approach in the realm of peripheral nerve injury (PNI) research. This article seeks to provide a comprehensive review of the latest advancements, applications, and mechanisms of action of four physical therapy modalities-ultrasound, electrical stimulation, photobiomodulation, and aerobic exercise-in the context of PNI. Ultrasound, characterized by its mechanical and thermal effects, is widely regarded as an effective non-invasive or minimally invasive method for neural modulation. Electrical stimulation therapy, a prevalent technique in PNI treatment, entails the application of electric currents to stimulate nerve and muscle tissues, thereby facilitating nerve regeneration and mitigating muscle atrophy. Photobiomodulation, a process that influences cell metabolism through the absorption of photon energy, is closely associated with neural regeneration in the field of rehabilitation medicine. Additionally, aerobic exercise, a popular form of physical activity, serves to enhance blood circulation and improve neuronal function. The article discusses various physical therapy methods for peripheral nerve injuries, including hyperbaric oxygen therapy, magnetic therapy, and biofeedback therapy, in addition to traditional approaches. Despite advancements, challenges in nerve injury treatment persist, such as the need for standardized treatment protocols, consideration of individual variations, and assessment of long-term effectiveness. Future research is needed to address these issues. In summary, this article offers theoretical and empirical evidence supporting the utilization of physical therapy in the management of PNI. This research aims to promote further research and clinical practice in this field, contributing to enhancing patient quality of life and recovery outcomes.
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Affiliation(s)
- Xiao-Lei Chu
- Department of Rehabilitation, Tianjin University Tianjin Hospital, Tianjin, China
| | - Xiao-Xuan Zhao
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Institute of Sport, Exercise and Health, Tianjin University of Sport, Tianjin, China
| | - Shuai-Yi Liu
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Institute of Sport, Exercise and Health, Tianjin University of Sport, Tianjin, China
| | - Ya-Jie Li
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Institute of Sport, Exercise and Health, Tianjin University of Sport, Tianjin, China
| | - Ning Ding
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Institute of Sport, Exercise and Health, Tianjin University of Sport, Tianjin, China
| | - Min-Qi Liu
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Institute of Sport, Exercise and Health, Tianjin University of Sport, Tianjin, China
| | - Qing-Wen Li
- Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Institute of Sport, Exercise and Health, Tianjin University of Sport, Tianjin, China
| | - Qi Li
- Department of Rehabilitation, Tianjin University Tianjin Hospital, Tianjin, China
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Henderson TA. Can infrared light really be doing what we claim it is doing? Infrared light penetration principles, practices, and limitations. Front Neurol 2024; 15:1398894. [PMID: 39263274 PMCID: PMC11388112 DOI: 10.3389/fneur.2024.1398894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 06/10/2024] [Indexed: 09/13/2024] Open
Abstract
Near infrared (NIR) light has been shown to provide beneficial treatment of traumatic brain injury (TBI) and other neurological problems. This concept has spawned a plethora of commercial entities and practitioners utilizing panels of light emitting diodes (LEDs) and promising to treat patients with TBI and other disorders, who are desperate for some treatment for their untreatable conditions. Unfortunately, an LED intended to deliver photonic energy to the human brain does not necessarily do what an LED pointed at a mouse brain does. There is a problem of scale. Extensive prior research has shown that infrared light from a 0.5-watt LED will not penetrate the scalp and skull of a human. Both the properties of NIR light and the manner in which it interacts with tissue are examined. Based on these principles, the shortcomings of current approaches to treating neurological disorders with NIR light are explored. Claims of clinical benefit from low-level LED-based devices are explored and the proof of concept challenged. To date, that proof is thin with marginal benefits which are largely transient. Extensive research has shown fluence at the level of the target tissue which falls within the range of 0.9 J/cm2 to 15 J/cm2 is most effective in activating the biological processes at the cellular level which underlie direct photobiomodulation. If low-level infrared light from LED devices is not penetrating the scalp and skull, then these devices certainly are not delivering that level of fluence to the neurons of the subjacent brain. Alternative mechanisms, such as remote photobiomodulation, which may underlie the small and transient benefits for TBI symptoms reported for low-power LED-based NIR studies are presented. Actionable recommendations for the field are offered.
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Affiliation(s)
- Theodore A Henderson
- Neuro-Luminance, Inc., Denver, CO, United States
- Neuro-Laser Foundation, Denver, CO, United States
- Dr. Theodore Henderson, Inc., Denver, CO, United States
- The Synaptic Space, Inc., Denver, CO, United States
- The International Society of Applied Neuroimaging (ISAN), Toronto, ON, Canada
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Ji Q, Yan S, Ding J, Zeng X, Liu Z, Zhou T, Wu Z, Wei W, Li H, Liu S, Ai S. Photobiomodulation improves depression symptoms: a systematic review and meta-analysis of randomized controlled trials. Front Psychiatry 2024; 14:1267415. [PMID: 38356614 PMCID: PMC10866010 DOI: 10.3389/fpsyt.2023.1267415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 10/26/2023] [Indexed: 02/16/2024] Open
Abstract
Background Depression is a common mental illness that is widely recognized by its lack of pleasure, fatigue, low mood, and, in severe cases, even suicidal tendencies. Photobiomodulation (PBM) is a non-invasive neuromodulation technique that could treat patients with mood disorders such as depression. Methods A systematic search of ten databases, including randomized controlled trials (RCTs) for depression, was conducted from the time of library construction to September 25, 2023. The primary outcome was depression. The secondary outcome was sleep. Meta-analysis was performed using RevMan (version 5.4) and Stata (version 14.0). Subgroup analyses were performed to identify sources of heterogeneity. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results Three thousand two hundred and sixty-five studies were retrieved from the database and screened for inclusion in eleven trials. The forest plot results demonstrated that PBM alleviated depression (SMD = -0.55, 95% CI [-0.75, -0.35], I2 = 46%). But it is not statistically significant for patients' sleep outcomes (SMD = -0.82, 95% CI [-2.41, 0.77], I2 = 0%, p > 0.05). Subgroup analysis showed that s-PBM was superior to t-PBM in relieving symptoms of depression. The best improvement for t-PBM was achieved using a wavelength of 823 nm, fluence of 10-100 J/cm2, irradiance of 50-100 mW/cm2, irradiance time of 30 min, treatment frequency < 3/week, and number of treatments >15 times. The best improvement for s-PBM was achieved using a wavelength of 808 nm, fluence ≤1 J/cm2, irradiance of 50-100 mW/cm2, irradiance time ≤ 5 min, treatment frequency ≥ 3/week, number of treatments >15 times. All results had evidence quality that was either moderate or very low, and there was no bias in publication. Conclusion We conclude that PBM is effective in reducing depression symptoms in patients. However, the current number of studies is small, and further studies are needed to extend the current analysis results. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, CRD42023444677.
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Affiliation(s)
- Qipei Ji
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shichang Yan
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jilin Ding
- Department of Rehabilitation, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, China
| | - Xin Zeng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Zhixiang Liu
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Tianqi Zhou
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhuorao Wu
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wei Wei
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Huaqiang Li
- School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shuangyue Liu
- Department of Rehabilitation, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, China
| | - Shuangchun Ai
- Department of Rehabilitation, Mianyang Hospital of Traditional Chinese Medicine, Mianyang, China
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Ramakrishnan P, Joshi A, Fazil M, Yadav P. A comprehensive review on therapeutic potentials of photobiomodulation for neurodegenerative disorders. Life Sci 2024; 336:122334. [PMID: 38061535 DOI: 10.1016/j.lfs.2023.122334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 12/02/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023]
Abstract
A series of experimental trials over the past two centuries has put forth Photobiomodulation (PBM) as a treatment modality that utilizes colored lights for various conditions. While in its cradle, PBM was used for treating simple conditions such as burns and wounds, advancements in recent years have extended the use of PBM for treating complex neurodegenerative diseases (NDDs). PBM has exhibited the potential to curb several symptoms and signs associated with NDDs. While several of the currently used therapeutics cause adverse side effects alongside being highly invasive, PBM on the contrary, seems to be broad-acting, less toxic, and non-invasive. Despite being projected as an ideal therapeutic for NDDs, PBM still isn't considered a mainstream treatment modality due to some of the challenges and knowledge gaps associated with it. Here, we review the advantages of PBM summarized above with an emphasis on the common mechanisms that underlie major NDDs and how PBM helps tackle them. We also discuss important questions such as whether PBM should be considered a mainstay treatment modality for these conditions and if PBM's properties can be harnessed to develop prophylactic therapies for high-risk individuals and also highlight important animal studies that underscore the importance of PBM and the challenges associated with it. Overall, this review is intended to bring the major advances made in the field to the spotlight alongside addressing the practicalities and caveats to develop PBM as a major therapeutic for NDDs.
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Affiliation(s)
- Pooja Ramakrishnan
- Fly Laboratory # 210, Anusandhan Kendra-II, School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur 613401, Tamil Nadu, India.
| | - Aradhana Joshi
- Fly Laboratory # 210, Anusandhan Kendra-II, School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur 613401, Tamil Nadu, India.
| | - Mohamed Fazil
- Fly Laboratory # 210, Anusandhan Kendra-II, School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur 613401, Tamil Nadu, India; School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur 613401, Tamil Nadu, India
| | - Pankaj Yadav
- Fly Laboratory # 210, Anusandhan Kendra-II, School of Chemical & Biotechnology, SASTRA Deemed to be University, Thanjavur 613401, Tamil Nadu, India.
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Baskerville R, Krijgsveld N, Esser P, Jeffery G, Poulton J. The Effect of Photobiomodulation on the Treatment of Hereditary Mitochondrial Diseases. J Lasers Med Sci 2023; 14:e41. [PMID: 38028882 PMCID: PMC10658120 DOI: 10.34172/jlms.2023.41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 08/07/2023] [Indexed: 12/01/2023]
Abstract
Introduction: Despite a wide variety of clinical presentations in hereditary Mitochondrial Diseases, muscle fatigue is a common theme and impairs a patient's quality of life and ability to function. Current treatments are only supportive and include nutritional supplementation and physical therapy. Photobiomodulation therapy (PBMT) using low-intensity, narrow spectrum light in the red/near infrared (NIR) range, from a low-level laser or light-emitting diode sources, enhances mitochondrial function in preclinical and clinical studies on a range of conditions. However, little research has been done on the effectiveness of photobiomodulation in hereditary mitochondrial disorders. Methods: We performed a scoping review of the evidence of the beneficial effects of photobiomodulation for treating the muscle-related symptoms of hereditary mitochondrial disease. Results: No studies regarding photobiomodulation in hereditary mitochondrial disease were identified. However, in other clinical conditions featuring acquired mitochondrial impairment, we identified studies that suggested improved function, although sample sizes were small in number and statistical power. Conclusion: There is emerging evidence of efficacy for PBMT for diseases involving acquired mitochondrial insufficiency. We identified no published research on PBMT in hereditary mitochondrial disease, but this review confirms a theoretical rationale for a positive effect and suggests further research.
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Affiliation(s)
| | | | - Patrick Esser
- Health and Life Sciences, Oxford Brookes University, Oxford, UK
| | - Glen Jeffery
- Institute of Ophthalmology, University College London, London, UK
| | - Joanna Poulton
- Hospital for Women and Reproductive Health, University of Oxford, Oxford, UK
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Li D, Liu S, Yu T, Liu Z, Sun S, Bragin D, Shirokov A, Navolokin N, Bragina O, Hu Z, Kurths J, Fedosov I, Blokhina I, Dubrovski A, Khorovodov A, Terskov A, Tzoy M, Semyachkina-Glushkovskaya O, Zhu D. Photostimulation of brain lymphatics in male newborn and adult rodents for therapy of intraventricular hemorrhage. Nat Commun 2023; 14:6104. [PMID: 37775549 PMCID: PMC10541888 DOI: 10.1038/s41467-023-41710-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 09/15/2023] [Indexed: 10/01/2023] Open
Abstract
Intraventricular hemorrhage is one of the most fatal forms of brain injury that is a common complication of premature infants. However, the therapy of this type of hemorrhage is limited, and new strategies are needed to reduce hematoma expansion. Here we show that the meningeal lymphatics is a pathway to remove red blood cells from the brain's ventricular system of male human, adult and newborn rodents and is a target for non-invasive transcranial near infrared photobiomodulation. Our results uncover the clinical significance of phototherapy of intraventricular hemorrhage in 4-day old male rat pups that have the brain similar to a preterm human brain. The course of phototherapy in newborn rats provides fast recovery after intraventricular hemorrhage due to photo-improvements of lymphatic drainage and clearing functions. These findings shed light on the mechanisms of phototherapy of intraventricular hemorrhage that can be a clinically relevant technology for treatment of neonatal intracerebral bleedings.
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Affiliation(s)
- Dongyu Li
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
- School of Optical Electronic Information, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
| | - Shaojun Liu
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
| | - Tingting Yu
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China.
| | - Zhang Liu
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
| | - Silin Sun
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
| | - Denis Bragin
- Lovelace Biomedical Research Institute, Albuquerque, NM, 87108, USA
- Department of Neurology University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA
| | - Alexander Shirokov
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Prospekt Entuziastov 13, Saratov, 410049, Russia
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia
| | - Nikita Navolokin
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia
- Saratov State Medical University, B. Kazachya str., 112, Saratov, 410012, Russia
| | - Olga Bragina
- Lovelace Biomedical Research Institute, Albuquerque, NM, 87108, USA
| | - Zhengwu Hu
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
- School of Optical Electronic Information, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China
| | - Jürgen Kurths
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia
- Physics Department, Humboldt University, Newtonstrasse 15, 12489, Berlin, Germany
- Potsdam Institute for Climate Impact Research, Telegrafenberg A31, 14473, Potsdam, Germany
- Sechenov First Moscow State Medical University, Bolshaya Pirogovskaya 2, building 4, 119435, Moscow, Russia
| | - Ivan Fedosov
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia
| | - Inna Blokhina
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia
| | | | | | - Andrey Terskov
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia
| | - Maria Tzoy
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia
| | - Oxana Semyachkina-Glushkovskaya
- Saratov State University, Astrakhanskaya str., 83, Saratov, 410012, Russia.
- Physics Department, Humboldt University, Newtonstrasse 15, 12489, Berlin, Germany.
| | - Dan Zhu
- Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, 430074, Wuhan, Hubei, China.
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Stevens AR, Hadis M, Milward M, Ahmed Z, Belli A, Palin W, Davies DJ. Photobiomodulation in Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis. J Neurotrauma 2023; 40:210-227. [PMID: 35698294 DOI: 10.1089/neu.2022.0140] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Photobiomodulation (PBM) is a therapeutic modality that has gained increasing interest in neuroscience applications, including acute traumatic brain injury (TBI). Its proposed mechanisms for therapeutic effect when delivered to the injured brain include antiapoptotic and anti-inflammatory effects. This systematic review summarizes the available evidence for the value of PBM in improving outcomes in acute TBI and presents a meta-analysis of the pre-clinical evidence for neurological severity score (NSS) and lesion size in animal models of TBI. A systematic review of the literature was performed, with searches and data extraction performed independently in duplicate by two authors. Eighteen published articles were identified for inclusion: seventeen pre-clinical studies of in vivo animal models and one clinical study in human patients. The available human study supports safety and feasibility of PBM in acute moderate TBI. For pre-clinical studies, meta-analysis for NSS and lesion size were found to favor intervention versus control. Subgroup analysis based on PBM parameter variables for these outcomes was performed. Favorable parameters were identified as: wavelengths in the region of 665 nm and 810 nm; time to first administration of PBM ≤4 h; total number of daily treatments ≤3. No differences were identified between pulsed and continuous wave modes or energy delivery. Mechanistic substudies within included in vivo studies are presented and were found to support hypotheses of antiapoptotic, anti-inflammatory, and pro-proliferative effects, and a modulation of cellular metabolism. This systematic review provides substantial meta-analysis evidence of the benefits of PBM on functional and histological outcomes of TBI in in vivo mammalian models. Study design and PBM parameters should be closely considered for future human clinical studies.
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Affiliation(s)
- Andrew Robert Stevens
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, and University of Birmingham, Edgbaston, Birmingham, United Kingdom.,NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham, United Kingdom.,Phototherapy Research Group, School of Dentistry, University of Birmingham, Birmingham, United Kingdom
| | - Mohammed Hadis
- Phototherapy Research Group, School of Dentistry, University of Birmingham, Birmingham, United Kingdom
| | - Michael Milward
- Phototherapy Research Group, School of Dentistry, University of Birmingham, Birmingham, United Kingdom
| | - Zubair Ahmed
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, and University of Birmingham, Edgbaston, Birmingham, United Kingdom.,NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham, United Kingdom.,Centre for Trauma Sciences Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Antonio Belli
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, and University of Birmingham, Edgbaston, Birmingham, United Kingdom.,NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham, United Kingdom.,Centre for Trauma Sciences Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom
| | - William Palin
- Phototherapy Research Group, School of Dentistry, University of Birmingham, Birmingham, United Kingdom
| | - David James Davies
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, and University of Birmingham, Edgbaston, Birmingham, United Kingdom.,NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham, United Kingdom.,Phototherapy Research Group, School of Dentistry, University of Birmingham, Birmingham, United Kingdom.,Centre for Trauma Sciences Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom
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Effects of Near-Infrared Light on Well-Being and Health in Human Subjects with Mild Sleep-Related Complaints: A Double-Blind, Randomized, Placebo-Controlled Study. BIOLOGY 2022; 12:biology12010060. [PMID: 36671752 PMCID: PMC9855677 DOI: 10.3390/biology12010060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/14/2022] [Accepted: 12/22/2022] [Indexed: 12/31/2022]
Abstract
Modern urban human activities are largely restricted to the indoors, deprived of direct sunlight containing visible and near-infrared (NIR) wavelengths at high irradiance levels. Therapeutic exposure to doses of red and NIR, known as photobiomodulation (PBM), has been effective for a broad range of conditions. In a double-blind, randomized, placebo-controlled study, we aimed to assess the effects of a PBM home set-up on various aspects of well-being, health, sleep, and circadian rhythms in healthy human subjects with mild sleep complaints. The effects of three NIR light (850 nm) doses (1, 4, or 6.5 J·cm-2) were examined against the placebo. Exposure was presented five days per week between 9:30 am and 12:30 pm for four consecutive weeks. The study was conducted in both summer and winter to include seasonal variation. The results showed PBM treatment only at 6.5 J·cm-2 to have consistent positive benefits on well-being and health, specifically improving mood, reducing drowsiness, reducing IFN-γ, and resting heart rate. This was only observed in winter. No significant effects on sleep or circadian rhythms were noted. This study provides further evidence that adequate exposure to NIR, especially during low sunlight conditions, such as in the winter, can be beneficial for human health and wellness.
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Nizamutdinov D, Ezeudu C, Wu E, Huang JH, Yi SS. Transcranial near-infrared light in treatment of neurodegenerative diseases. Front Pharmacol 2022; 13:965788. [PMID: 36034819 PMCID: PMC9400541 DOI: 10.3389/fphar.2022.965788] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/12/2022] [Indexed: 11/13/2022] Open
Abstract
Light is a natural agent consisting of a range of visible and invisible electromagnetic spectrum travels in waves. Near-infrared (NIR) light refers to wavelengths from 800 to 2,500 nm. It is an invisible spectrum to naked eyes and can penetrate through soft and hard tissues into deep structures of the human body at specific wavelengths. NIR light may carry different energy levels depending on the intensity of emitted light and therapeutic spectrum (wavelength). Stimulation with NIR light can activate intracellular cascades of biochemical reactions with local short- and long-term positive effects. These properties of NIR light are employed in photobiomodulation (PBM) therapy, have been linked to treating several brain pathologies, and are attracting more scientific attention in biomedicine. Transcranial brain stimulations with NIR light PBM in recent animal and human studies revealed a positive impact of treatment on the progression and improvement of neurodegenerative processes, management of brain energy metabolism, and regulation of chronic brain inflammation associated with various conditions, including traumatic brain injury. This scientific overview incorporates the most recent cellular and functional findings in PBM with NIR light in treating neurodegenerative diseases, presents the discussion of the proposed mechanisms of action, and describes the benefits of this treatment in neuroprotection, cell preservation/detoxification, anti-inflammatory properties, and regulation of brain energy metabolism. This review will also discuss the novel aspects and pathophysiological role of the glymphatic and brain lymphatics system in treating neurodegenerative diseases with NIR light stimulations. Scientific evidence presented in this overview will support a combined effort in the scientific community to increase attention to the understudied NIR light area of research as a natural agent in the treatment of neurodegenerative diseases to promote more research and raise awareness of PBM in the treatment of brain disorders.
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Affiliation(s)
- Damir Nizamutdinov
- Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, TX, United States
- Texas A&M University, College of Medicine, Neurosurgery, TX, United States
| | - Chibueze Ezeudu
- Texas A&M University, College of Medicine, Neurosurgery, TX, United States
| | - Erxi Wu
- Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, TX, United States
- Texas A&M University, College of Medicine, Neurosurgery, TX, United States
- Texas A&M University, School of Pharmacy, Pharmaceutical Sciences, TX, United States
- Department of Oncology, Dell Medical School, The University of Texas at Austin, TX, United States
| | - Jason H. Huang
- Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, TX, United States
- Texas A&M University, College of Medicine, Neurosurgery, TX, United States
- *Correspondence: S. Stephen Yi, ; Jason H. Huang,
| | - S. Stephen Yi
- Department of Oncology, Dell Medical School, The University of Texas at Austin, TX, United States
- *Correspondence: S. Stephen Yi, ; Jason H. Huang,
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11
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Pavel DG, Henderson TA, DeBruin S, Cohen PF. The Legacy of the TTASAAN Report - Premature Conclusions and Forgotten Promises About SPECT Neuroimaging: A Review of Policy and Practice Part II. Front Neurol 2022; 13:851609. [PMID: 35655621 PMCID: PMC9152128 DOI: 10.3389/fneur.2022.851609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 02/28/2022] [Indexed: 11/29/2022] Open
Abstract
Brain perfusion single photon emission computed tomography (SPECT) scans were initially developed in 1970s. A key radiopharmaceutical, hexamethylpropyleneamine oxime (HMPAO), was not stabilized until 1993 and most early SPECT scans were performed on single-head gamma cameras. These early scans were of inferior quality. In 1996, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (TTASAAN) issued a report regarding the use of SPECT in the evaluation of neurological disorders. This two-part series explores the policies and procedures related to perfusion SPECT functional neuroimaging. In Part I, the comparison between the quality of the SPECT scans and the depth of the data for key neurological and psychiatric indications at the time of the TTASAAN report vs. the intervening 25 years were presented. In Part II, the technical aspects of perfusion SPECT neuroimaging and image processing will be explored. The role of color scales will be reviewed and the process of interpreting a SPECT scan will be presented. Interpretation of a functional brain scans requires not only anatomical knowledge, but also technical understanding on correctly performing a scan, regardless of the scanning modality. Awareness of technical limitations allows the clinician to properly interpret a functional brain scan. With this foundation, four scenarios in which perfusion SPECT neuroimaging, together with other imaging modalities and testing, lead to a narrowing of the differential diagnoses and better treatment. Lastly, recommendations for the revision of current policies and practices are made.
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Affiliation(s)
- Dan G Pavel
- PathFinder Brain SPECT, Deerfield, IL, United States.,The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States
| | - Theodore A Henderson
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,The Synaptic Space, Inc., Denver, CO, United States.,Neuro-Luminance, Inc., Denver, CO, United States.,Dr. Theodore Henderson, Inc., Denver, CO, United States.,Neuro-Laser Foundation, Denver, CO, United States
| | - Simon DeBruin
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,Good Lion Imaging, Baltimore, MD, United States
| | - Philip F Cohen
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,Nuclear Medicine, Lions Gate Hospital, Vancouver, BC, Canada.,Department of Radiology, University of British Columbia, Vancouver, BC, Canada
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12
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Pavel DG, Henderson TA, DeBruin S. The Legacy of the TTASAAN Report-Premature Conclusions and Forgotten Promises: A Review of Policy and Practice Part I. Front Neurol 2022; 12:749579. [PMID: 35450131 PMCID: PMC9017602 DOI: 10.3389/fneur.2021.749579] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 12/14/2021] [Indexed: 12/20/2022] Open
Abstract
Brain perfusion single photon emission computed tomography (SPECT) scans were initially developed in 1970's. A key radiopharmaceutical, hexamethylpropyleneamine oxime (HMPAO), was originally approved in 1988, but was unstable. As a result, the quality of SPECT images varied greatly based on technique until 1993, when a method of stabilizing HMPAO was developed. In addition, most SPECT perfusion studies pre-1996 were performed on single-head gamma cameras. In 1996, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (TTASAAN) issued a report regarding the use of SPECT in the evaluation of neurological disorders. Although the TTASAAN report was published in January 1996, it was approved for publication in October 1994. Consequently, the reported brain SPECT studies relied upon to derive the conclusions of the TTASAAN report largely pre-date the introduction of stabilized HMPAO. While only 12% of the studies on traumatic brain injury (TBI) in the TTASAAN report utilized stable tracers and multi-head cameras, 69 subsequent studies with more than 23,000 subjects describe the utility of perfusion SPECT scans in the evaluation of TBI. Similarly, dementia SPECT imaging has improved. Modern SPECT utilizing multi-headed gamma cameras and quantitative analysis has a sensitivity of 86% and a specificity of 89% for the diagnosis of mild to moderate Alzheimer's disease-comparable to fluorodeoxyglucose positron emission tomography. Advances also have occurred in seizure neuroimaging. Lastly, developments in SPECT imaging of neurotoxicity and neuropsychiatric disorders have been striking. At the 25-year anniversary of the publication of the TTASAAN report, it is time to re-examine the utility of perfusion SPECT brain imaging. Herein, we review studies cited by the TTASAAN report vs. current brain SPECT imaging research literature for the major indications addressed in the report, as well as for emerging indications. In Part II, we elaborate technical aspects of SPECT neuroimaging and discuss scan interpretation for the clinician.
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Affiliation(s)
- Dan G Pavel
- Pathfinder Brain SPECT Imaging, Deerfield, IL, United States.,The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States
| | - Theodore A Henderson
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,The Synaptic Space, Inc., Denver, CO, United States.,Neuro-Luminance, Inc., Denver, CO, United States.,Dr. Theodore Henderson, Inc., Denver, CO, United States
| | - Simon DeBruin
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,Good Lion Imaging, Columbia, SC, United States
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13
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Yang L, Wu C, Parker E, Li Y, Dong Y, Tucker L, Brann DW, Lin HW, Zhang Q. Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model. Theranostics 2022; 12:2205-2231. [PMID: 35265207 PMCID: PMC8899582 DOI: 10.7150/thno.70756] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 01/28/2022] [Indexed: 11/05/2022] Open
Abstract
Alzheimer's disease (AD) is the most common form of dementia in the elderly, causing neuronal degeneration and cognitive deficits that significantly impair independence and quality of life for those affected and their families. Though AD is a major neurodegenerative disease with vast avenues of investigation, there is no effective treatment to cure AD or slow disease progression. The present work evaluated the therapeutic effect of long-term photobiomodulation (PBM) treatment with continuous-wave low-level laser on AD and its underlying mechanism. Methods: PBM was implemented for 2 min, 3 times per week for 16 months in 2-month-old transgenic AD rats. A battery of behavioral tests was performed to measure the effect of PBM treatment on cognitive dysfunction in AD rats. The effects of PBM therapy on typical AD pathologies, including amyloid plaques, intracellular neurofibrillary tangles, neuronal loss, neuronal injury, neuronal apoptosis, and neurodegeneration, were then assessed. The underlying mechanisms were measured using immunofluorescence staining, western blotting analysis, mass spectrometry, primary cortical and hippocampal cell cultures, and related assay kits. Results: PBM treatment significantly improved the typical AD pathologies of memory loss, amyloid plaques, tau hyperphosphorylation, neuronal degeneration, spine damage, and synaptic loss. PBM treatment had several mechanistic effects which may explain these beneficial effects, including 1) regulation of glial cell polarization and inhibition of neuroinflammation, 2) preservation of mitochondrial dynamics by regulating fission and fusion proteins, and 3) suppression of oxidative damage to DNA, proteins, and lipids. Furthermore, PBM enhanced recruitment of microglia surrounding amyloid plaques by improving the expression of microglial IL-3Rα and astrocytic IL-3, which implies a potential role of PBM in improving Aβ clearance. Finally, our results implicate neuronal hemoglobin in mediating the neuroprotective effect of PBM, as Hbα knockdown abolished the neuroprotective effect of PBM treatment. Conclusion: Collectively, our data supports the potential use of PBM treatment to prevent or slow the progression of AD and provides new insights into the molecular mechanisms of PBM therapy.
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Affiliation(s)
- Luodan Yang
- Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, 1501 Kings Highway, LA 71103 USA
- Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA
| | - Chongyun Wu
- Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA
| | - Emily Parker
- Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA
| | - Yong Li
- Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA
| | - Yan Dong
- Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA
| | - Lorelei Tucker
- Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA
| | - Darrell W. Brann
- Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA
| | - Hung Wen Lin
- Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, 1501 Kings Highway, LA 71103 USA
| | - Quanguang Zhang
- Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, 1501 Kings Highway, LA 71103 USA
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Kong LZ, Zhang RL, Hu SH, Lai JB. Military traumatic brain injury: a challenge straddling neurology and psychiatry. Mil Med Res 2022; 9:2. [PMID: 34991734 PMCID: PMC8740337 DOI: 10.1186/s40779-021-00363-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 12/27/2021] [Indexed: 12/12/2022] Open
Abstract
Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury (TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood-brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.
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Affiliation(s)
- Ling-Zhuo Kong
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Rui-Li Zhang
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shao-Hua Hu
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. .,The Key Laboratory of Mental Disorder's Management in Zhejiang Province, Hangzhou, 310003, China. .,Brain Research Institute of Zhejiang University, Hangzhou, 310003, China. .,Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, 310003, China. .,MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University, Hangzhou, 310003, China.
| | - Jian-Bo Lai
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. .,The Key Laboratory of Mental Disorder's Management in Zhejiang Province, Hangzhou, 310003, China. .,Brain Research Institute of Zhejiang University, Hangzhou, 310003, China. .,Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, 310003, China. .,MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University, Hangzhou, 310003, China.
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15
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Henderson TA, Cohen PF, Cardaci G, Urbain JLC. Editorial: The Emerging Role of SPECT Functional Neuroimaging in Psychiatry & Neurology. Front Psychiatry 2022; 13:928653. [PMID: 35859601 PMCID: PMC9289600 DOI: 10.3389/fpsyt.2022.928653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 05/16/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Theodore A Henderson
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,The Synaptic Space, Inc., Denver, CO, United States.,Neuro-Luminance, Inc., Denver, CO, United States.,Dr. Theodore Henderson, Inc., Denver, CO, United States.,Neuro-Laser Foundation, Denver, CO, United States
| | - Philip F Cohen
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,Nuclear Medicine, Lions Gate Hospital, Vancouver, BC, Canada.,Department of Radiology, University of British Columbia, Vancouver, BC, Canada
| | - Giuseppe Cardaci
- The International Society of Applied Neuroimaging (ISAN), Denver, CO, United States.,University of Notre Dame, Fremantle, WA, Australia
| | - Jean-Luc C Urbain
- Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United States.,Department of Nuclear Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States
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16
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Perez Garcia G, Perez GM, Otero-Pagan A, Abutarboush R, Kawoos U, De Gasperi R, Gama Sosa MA, Pryor D, Hof PR, Cook DG, Gandy S, Ahlers ST, Elder GA. Transcranial Laser Therapy Does Not Improve Cognitive and Post-Traumatic Stress Disorder-Related Behavioral Traits in Rats Exposed to Repetitive Low-Level Blast Injury. Neurotrauma Rep 2021; 2:548-563. [PMID: 34901948 PMCID: PMC8655798 DOI: 10.1089/neur.2021.0005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Many military veterans who experienced blast-related traumatic brain injuries (TBIs) in the conflicts in Iraq and Afghanistan suffer from chronic cognitive and mental health problems, including post-traumatic stress disorder (PTSD). Transcranial laser therapy (TLT) uses low-power lasers emitting light in the far- to near-infrared ranges. Beneficial effects of TLT have been reported in neurological and mental-health-related disorders in humans and animal models, including TBI. Rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits. We tested whether TLT treatment could reverse these traits. Rats received a 74.5-kPa blast or sham exposures delivered one per day for 3 consecutive days. Beginning at 34 weeks after blast exposure, the following groups of rats were treated with active or sham TLT: 1) Sham-exposed rats (n = 12) were treated with sham TLT; 2) blast-exposed rats (n = 13) were treated with sham TLT; and 3) blast-exposed rats (n = 14) were treated with active TLT. Rats received 5 min of TLT five times per week for 6 weeks (wavelength, 808 nm; power of irradiance, 240 mW). At the end of treatment, rats were tested in tasks found previously to be most informative (novel object recognition, novel object localization, contextual/cued fear conditioning, elevated zero maze, and light/dark emergence). TLT did not improve blast-related effects in any of these tests, and blast-exposed rats were worse after TLT in some anxiety-related measures. Based on these findings, TLT does not appear to be a promising treatment for the chronic cognitive and mental health problems that follow blast injury.
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Affiliation(s)
- Georgina Perez Garcia
- Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Gissel M. Perez
- Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
| | - Alena Otero-Pagan
- Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
| | - Rania Abutarboush
- Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA
| | - Usmah Kawoos
- Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA
| | - Rita De Gasperi
- Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Miguel A. Gama Sosa
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
| | - Dylan Pryor
- Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
| | - Patrick R. Hof
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - David G. Cook
- Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, USA
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Sam Gandy
- Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Barbara and Maurice A. Deane Center for Wellness and Cognitive Health and the Mount Sinai NFL Neurological Care Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Stephen T. Ahlers
- Department of Neurotrauma, Naval Medical Research Center, Silver Spring, Maryland, USA
| | - Gregory A. Elder
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA
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Onose G, Anghelescu A, Blendea CD, Ciobanu V, Daia CO, Firan FC, Munteanu C, Oprea M, Spinu A, Popescu C. Non-invasive, non-pharmacological/bio-technological interventions towards neurorestoration upshot after ischemic stroke, in adults-systematic, synthetic, literature review. FRONT BIOSCI-LANDMRK 2021; 26:1204-1239. [PMID: 34856764 DOI: 10.52586/5020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/02/2021] [Accepted: 10/20/2021] [Indexed: 11/09/2022]
Abstract
Considering its marked life-threatening and (not seldom: severe and/or permanent) disabling, potential, plus the overall medico-psycho-socio-economic tough burden it represents for the affected persons, their families and the community, the cerebrovascular accident (CVA)-including with the, by far more frequent, ischemic type-is subject to considerable scientific research efforts that aim (if possible) at eliminating the stroke induced lesions, and consist, as well, in ambitious-but still poorly transferable into medical practice-goals such as brain neuroregeneration and/or repair, within related corollary/upshot of neurorestoration. We have conducted, in this respect, a systematic and synthetic literature review, following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" concept. Accordingly, we have interrogated five internationally renowned medical data bases: Elsevier, NCBI/PubMed, NCBI/PMC, PEDro, and ISI Web of Knowledge/Science (the last one to check whether the initially identified articles are published in ISI indexed journals), based on a large (details in the body text) number of most appropriate, to our knowledge, key word combinations/"syntaxes"-used contextually-and subsequently fulfilling the related, on five steps, filtering/selection methodology. We have thereby selected 114 fully eligible (of which contributive: 83-see further) papers; at the same time, additionally, we have enhanced our documentation-basically, but not exclusively, for the introductive part of this work (see further)-with bibliographic resources, overall connected to our subject, identified in the literature within a non-standardized search. It appears that the opportunity window for morph-functional recovery after stroke is larger than previously thought, actually being considered that brain neurorestoration/repair could occur, and therefore be expected, in later stages than in earlier ones, although, in this context, the number of cases possibly benefitting (for instance after physical and/or cognitive rehabilitation-including with magnetic or direct current transcranial stimulation) is quite small and with more or less conflicting, related outcomes, in the literature. Moreover, applying especially high intense, solicitating, rehabilitation interventions, in early stages post (including ischemic) stroke could even worsen the functional evolution. Accordingly, for clarifications and validation of more unitary points of view, continuing and boosting research efforts in this complex, interdisciplinary domain, is necessary. Until finding (if ever) effective modalities to cure the lesions of the central nervous system (CNS)-including post ischemic stroke-it is reasonable and recommendable-based on rigorous methodologies-the avail of combined ways: physiatric, pharmacologic, possibly also bio-technologic. On a different note, but however connected to our subject: periodic related systematic, synthetic literature reviews reappraisals are warranted and welcome.
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Affiliation(s)
- Gelu Onose
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Aurelian Anghelescu
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
- Specific Disciplines Department, Faculty of Midwifes and Nursing, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
| | - Corneliu Dan Blendea
- Medical-Surgical and Prophylactic Disciplines Department - Medical Rehabilitation, Recovery and Medical Physical Culture Discipline, Faculty of Medicine, University "Titu Maiorescu", 040051 Bucharest, Romania
- Physical and Rehabilitation Medicine & Balneology Clinic Division - The Neuro-Rehabilitation Compartment, Teaching Emergency Hospital of the Ilfov County, 22104 Bucharest, Romania
| | - Vlad Ciobanu
- Politehnica University of Bucharest, Computer Science Department, 060042 Bucharest, Romania
| | - Cristina Octaviana Daia
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Florentina Carmen Firan
- Physical and Rehabilitation Medicine & Balneology Clinic Division - The Neuro-Rehabilitation Compartment, Teaching Emergency Hospital of the Ilfov County, 22104 Bucharest, Romania
| | - Constantin Munteanu
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
- Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy "Grigore T. Popa" Iasi, 700454 Iasi, Romania
| | - Mihaela Oprea
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Aura Spinu
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Cristina Popescu
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
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Wang X, Li X, Zuo X, Liang Z, Ding T, Li K, Ma Y, Li P, Zhu Z, Ju C, Zhang Z, Song Z, Quan H, Zhang J, Hu X, Wang Z. Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats. J Neuroinflammation 2021; 18:256. [PMID: 34740378 PMCID: PMC8571847 DOI: 10.1186/s12974-021-02312-x] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 10/29/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. METHODS Male Sprague-Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. RESULTS PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. CONCLUSION Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.
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Affiliation(s)
- Xuankang Wang
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Xin Li
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.,967 Hospital of People's Liberation Army Joint Logistic Support Force, Dalian, 116044, Liaoning, China
| | - Xiaoshuang Zuo
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Zhuowen Liang
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Tan Ding
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Kun Li
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Yangguang Ma
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Penghui Li
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Zhijie Zhu
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Cheng Ju
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Zhihao Zhang
- 967 Hospital of People's Liberation Army Joint Logistic Support Force, Dalian, 116044, Liaoning, China
| | - Zhiwen Song
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Huilin Quan
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Jiawei Zhang
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Xueyu Hu
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Zhe Wang
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
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19
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Salehpour F, Gholipour-Khalili S, Farajdokht F, Kamari F, Walski T, Hamblin MR, DiDuro JO, Cassano P. Therapeutic potential of intranasal photobiomodulation therapy for neurological and neuropsychiatric disorders: a narrative review. Rev Neurosci 2021; 31:269-286. [PMID: 31812948 DOI: 10.1515/revneuro-2019-0063] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 09/22/2019] [Indexed: 12/25/2022]
Abstract
The application of photobiomodulation therapy (PBMT) for neuronal stimulation is studied in different animal models and in humans, and has shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and potential method for the treatment of brain conditions. Herein, we provide a summary of different intranasal light delivery approaches including a nostril-based portable method and implanted deep-nasal methods for the effective systemic or direct irradiation of the brain. Nostril-based i-PBMT devices are available, using either lasers or light emitting diodes (LEDs), and can be applied either alone or in combination to transcranial devices (the latter applied directly to the scalp) to treat a wide range of brain conditions such as mild cognitive impairment, Alzheimer's disease, Parkinson's disease, cerebrovascular diseases, depression and anxiety as well as insomnia. Evidence shows that nostril-based i-PBMT improves blood rheology and cerebral blood flow, so that, without needing to puncture blood vessels, i-PBMT may have equivalent results to a peripheral intravenous laser irradiation procedure. Up to now, no studies were conducted to implant PBMT light sources deep within the nose in a clinical setting, but simulation studies suggest that deep-nasal PBMT via cribriform plate and sphenoid sinus might be an effective method to deliver light to the ventromedial part of the prefrontal and orbitofrontal cortex. Home-based i-PBMT, using inexpensive LED applicators, has potential as a novel approach for neurorehabilitation; comparative studies also testing sham, and transcranial PBMT are warranted.
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Affiliation(s)
- Farzad Salehpour
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz 5166614756, Iran.,NiraxxLight Therapeutics, Irvine, CA 92617, USA.,ProNeuroLIGHT LLC, 3504 W Buckhorn Trail, Phoenix, AZ 85083, USA
| | - Sevda Gholipour-Khalili
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz 5166614756, Iran
| | - Fereshteh Farajdokht
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz 5166614756, Iran
| | - Farzin Kamari
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz 5166614756, Iran
| | - Tomasz Walski
- Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Galway H91 W2TY, Ireland.,Department of Biomedical Engineering, Wrocław University of Science and Technology, Wrocław 50-370, Poland
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA.,Department of Dermatology, Harvard Medical School, 40 Blossom St, Boston, MA 02114, USA.,Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
| | - Joseph O DiDuro
- ProNeuroLIGHT LLC, 3504 W Buckhorn Trail, Phoenix, AZ 85083, USA.,Neuropathy Treatment Centers of America LLC, Phoenix, AZ, USA
| | - Paolo Cassano
- Department of Psychiatry, Harvard Medical School, Boston, MA 02114, USA.,Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Bowdoin Square, Boston, MA 02114, USA.,Center for Anxiety and Traumatic Stress Disorders, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA
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20
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Nizamutdinov D, Qi X, Berman MH, Dougal G, Dayawansa S, Wu E, Yi SS, Stevens AB, Huang JH. Transcranial Near Infrared Light Stimulations Improve Cognition in Patients with Dementia. Aging Dis 2021; 12:954-963. [PMID: 34221541 PMCID: PMC8219492 DOI: 10.14336/ad.2021.0229] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 03/01/2021] [Indexed: 01/13/2023] Open
Abstract
Dementia is a complex syndrome with various presentations depending on the underlying pathologies. Low emission of transcranial near-infrared (tNIR) light can reach human brain parenchyma and be beneficial to a number of neurological and neurodegenerative disorders. We hereby examined the safety and potential therapeutic benefits of tNIR light stimulations in the treatment of dementia. Patients of mild to moderate dementia were randomized into active and sham treatment groups at 2:1 ratio. Active treatment consisted of low power tNIR light stimulations with an active photobiomodulation for 6 min twice daily during 8 consequent weeks. Sham treatment consisted of same treatment routine with a sham device. Neuropsychological battery was obtained before and after treatment. Analysis of variance (ANOVA) was used to analyze outcomes. Sixty subjects were enrolled. Fifty-seven subjects completed the study and had not reported health or adverse side effects during or after the treatment. Three subjects dropped out from trial for health issues unrelated to use of tNIR light treatment. Treatment with active device resulted in improvements of cognitive functions and changes were: an average increase of MMSE by 4.8 points; Logical Memory Tests I and II by ~3.0 points; Trail Making Tests A and B by ~24%; Boston Naming Test by ~9%; improvement of both Auditory Verbal Learning Tests in all subtest categories and overall time of performance. Many patients reported improved sleep after ~7 days of treatment. Caregivers noted that patients had less anxiety, improved mood, energy, and positive daily routine after ~14-21 days of treatment. The tNIR light treatments demonstrated safety and positive cognitive improvements in patients with dementia. Developed treatment protocol can be conveniently used at home. This study suggests that additional dementia treatment trials are warranted with a focus on mitigating caregivers’ burden with tNIR light treatment of dementia patients.
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Affiliation(s)
- Damir Nizamutdinov
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA
| | - Xiaoming Qi
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA
| | | | | | - Samantha Dayawansa
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA
| | - Erxi Wu
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA.,5Texas A&M University, HSC, College of Pharmacy, Department of Pharmaceutical Sciences, College Station, TX, USA.,6Department of Oncology, Dell Medical School, The University of Texas at Austin, TX, USA
| | - S Stephen Yi
- 6Department of Oncology, Dell Medical School, The University of Texas at Austin, TX, USA
| | - Alan B Stevens
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA
| | - Jason H Huang
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA
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21
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Chan AS, Lee TL, Hamblin MR, Cheung MC. Photoneuromodulation makes a difficult cognitive task less arduous. Sci Rep 2021; 11:13688. [PMID: 34211101 PMCID: PMC8249594 DOI: 10.1038/s41598-021-93228-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 06/21/2021] [Indexed: 12/04/2022] Open
Abstract
A positive effect of photoneuromodulation (PNM) has been found on cognitive and emotional functions in healthy populations. However, the hemodynamic changes associated with improved cognitive functions (i.e., memory and executive functions) are unexplored. Therefore, the present study investigated the hemodynamic changes associated with PNM using functional near-infrared spectroscopy (fNIRS). In this experiment, 33 young healthy adults were recruited and randomly assigned to control and experimental groups. A single PNM stimulation was applied to the forehead in the experimental group, while a sham stimulation (same procedure without machine activation) was performed for the control group. Before and after the stimulation, all participants performed an n-back task with 0-and 3-back conditions to assess their working memory function, and their hemodynamic responses during the tasks were measured by fNIRS. A significant group (experimental vs. control) × time (before vs. after PNM) interaction in memory-related frontal activation was found. Specifically, only the experimental group had a significant reduction in frontal hemodynamic levels during the difficult task. Additionally, the memory-related frontal activation was significantly correlated with the immediate and delayed recall of the Rey–Osterrieth Complex Figure Test assessed at baseline. Therefore, PNM may reduce the cognitive efforts needed to complete tasks with high memory loads.
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Affiliation(s)
- Agnes S Chan
- Department of Psychology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. .,Research Center for Neuropsychological Well-Being, The Chinese University of Hong Kong, Hong Kong, China.
| | - Tsz-Lok Lee
- Department of Psychology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa.,Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mei-Chun Cheung
- Department of Social Work, The Chinese University of Hong Kong, Hong Kong, China
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22
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Yang M, Yang Z, Wang P, Sun Z. Current application and future directions of photobiomodulation in central nervous diseases. Neural Regen Res 2021; 16:1177-1185. [PMID: 33269767 PMCID: PMC8224127 DOI: 10.4103/1673-5374.300486] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/20/2020] [Accepted: 05/25/2020] [Indexed: 02/05/2023] Open
Abstract
Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions. Photobiomodulation can promote neurogenesis and elicit anti-apoptotic, anti-inflammatory and antioxidative responses. Its therapeutic effects have been demonstrated in studies on neurological diseases, peripheral nerve injuries, pain relief and wound healing. We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019. The NCBI PubMed database, EMBASE database, Cochrane Library and ScienceDirect database were searched. We reviewed 95 papers and analyzed. Photobiomodulation has wide applicability in the treatment of stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, major depressive disorder, and other diseases. Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases. However, additional studies with adequate sample size are needed to optimize treatment parameters.
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Affiliation(s)
- Muyue Yang
- Shanghai Jiao Tong University, Shanghai, China
| | - Zhen Yang
- Core Facility of West China Hospital, Chengdu, Sichuan Province, China
| | - Pu Wang
- Department of Rehabilitation Medicine, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong Province, China
| | - Zhihui Sun
- Department of Psychosomatic Medicine, The People’s Hospital of Suzhou New District, Suzhou, Jiangsu Province, China
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23
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Shah EJ, Hüttemann M, Sanderson TH, Gurdziel K, Ruden DM. Inhibiting Mitochondrial Cytochrome c Oxidase Downregulates Gene Transcription After Traumatic Brain Injury in Drosophila. Front Physiol 2021; 12:628777. [PMID: 33790803 PMCID: PMC8005633 DOI: 10.3389/fphys.2021.628777] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 02/23/2021] [Indexed: 12/13/2022] Open
Abstract
Traumatic brain injuries (TBIs) caused by a sudden impact to the head alter behavior and impair physical and cognitive function. Besides the severity, type and area of the brain affected, the outcome of TBI is also influenced by the patient’s biological sex. Previous studies reporting mitochondrial dysfunction mainly focused on exponential reactive oxygen species (ROS) generation, increased mitochondrial membrane potential, and altered mitochondrial dynamics as a key player in the outcome to brain injury. In this study, we evaluated the effect of a near-infrared (NIR) light exposure on gene expression in a Drosophila TBI model. NIR interacts with cytochrome c oxidase (COX) of the electron transport chain to reduce mitochondrial membrane potential hyperpolarization, attenuate ROS generation, and apoptosis. We subjected w1118 male and female flies to TBI using a high-impact trauma (HIT) device and subsequently exposed the isolated fly brains to a COX-inhibitory wavelength of 750 nm for 2 hours (hr). Genome-wide 3′-mRNA-sequencing of fly brains revealed that injured w1118 females exhibit greater changes in transcription compared to males at 1, 2, and 4 hours (hr) after TBI. Inhibiting COX by exposure to NIR downregulates gene expression in injured females but has minimal effect in injured males. Our results suggest that mitochondrial COX modulation with NIR alters gene expression in Drosophila following TBI and the response to injury and NIR exposure varies by biological sex.
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Affiliation(s)
- Ekta J Shah
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States
| | - Maik Hüttemann
- Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, United States
| | - Thomas H Sanderson
- Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Katherine Gurdziel
- Office of the Vice President of Research, Wayne State University, Detroit, MI, United States
| | - Douglas M Ruden
- Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, United States.,Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, United States.,Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, United States
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24
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Chen H, Wang Y, Tu W, Wang H, Yin H, Sha H, Li Y. Effects of photobiomodulation combined with MSCs transplantation on the repair of spinal cord injury in rat. J Cell Physiol 2021; 236:921-930. [PMID: 32583437 DOI: 10.1002/jcp.29902] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 06/14/2020] [Accepted: 06/14/2020] [Indexed: 12/26/2022]
Abstract
Stem cell transplantation has shown promising regenerative effects against neural injury, and photobiomodulation (PBM) can aid tissue recovery. This study aims to evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and laser alone or combined on spinal cord injury (SCI). The animals were divided into SCI, hUCMSCs, laser treatment (LASER) and combination treatment (hUCMSCs + LASER) groups. Cell-enriched grafts of hUCMSCs (1 × 106 cells/ml) were injected at the site of antecedent trauma in SCI model rats. A 2 cm2 damaged area was irradiated with 630 nm laser at 100 mW/cm2 power for 20 min. Locomotion was evaluated using Basso-Beattie-Bresnahan (BBB) scores, and neurofilament repair were monitored by histological staining and diffusion tensor imaging (DTI). First, after SCI, the motor function of each group was restored with different degrees, the combination treatment significantly increased the BBB scores compared to either monotherapy. In addition, Nissl bodies were more numerous, and the nerve fibers were longer and thicker in the combination treatment group. Consistent with this, the in situ expression of NF-200 and glial fibrillary acidic protein in the damaged area was the highest in the combination treatment group. Finally, DTI showed that the combination therapy optimally improved neurofilament structure and arrangement. These results may show that the combination of PBM and hUCMSCs transplantation is a feasible strategy for reducing secondary damage and promoting functional recovery following SCI.
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Affiliation(s)
- Hongli Chen
- School of Life Sciences, Tiangong University, Tianjin, China
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
| | - Yunhao Wang
- School of Life Sciences, Tiangong University, Tianjin, China
| | - Wenjun Tu
- School of Life Sciences, Tiangong University, Tianjin, China
- Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
| | - Hong Wang
- School of Life Sciences, Tiangong University, Tianjin, China
- Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
| | - Huijuan Yin
- Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
| | - Hong Sha
- Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
| | - Yingxin Li
- Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
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25
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Dos Santos Cardoso F, Dos Santos JCC, Gonzalez-Lima F, Araújo BHS, Lopes-Martins RÁB, Gomes da Silva S. Effects of Chronic Photobiomodulation with Transcranial Near-Infrared Laser on Brain Metabolomics of Young and Aged Rats. Mol Neurobiol 2021; 58:2256-2268. [PMID: 33417219 DOI: 10.1007/s12035-020-02247-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 12/03/2020] [Indexed: 12/25/2022]
Abstract
Since laser photobiomodulation has been found to enhance brain energy metabolism and cognition, we conducted the first metabolomics study to systematically analyze the metabolites modified by brain photobiomodulation. Aging is often accompanied by cognitive decline and susceptibility to neurodegeneration, including deficits in brain energy metabolism and increased susceptibility of nerve cells to oxidative stress. Changes in oxidative stress and energetic homeostasis increase neuronal vulnerability, as observed in diseases related to brain aging. We evaluated and compared the cortical and hippocampal metabolic pathways of young (4 months old) and aged (20 months old) control rats with those of rats exposed to transcranial near-infrared laser over 58 consecutive days. Statistical analyses of the brain metabolomics data indicated that chronic transcranial photobiomodulation (1) significantly enhances the metabolic pathways of young rats, particularly for excitatory neurotransmission and oxidative metabolism, and (2) restores the altered metabolic pathways of aged rats towards levels found in younger rats, mainly in the cerebral cortex. These novel metabolomics findings may help complement other laser-induced neurocognitive, neuroprotective, anti-inflammatory, and antioxidant effects described in the literature.
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Affiliation(s)
- Fabrízio Dos Santos Cardoso
- Núcleo de Pesquisas Tecnológicas, Universidade de Mogi das Cruzes, Av. Cândido Xavier de Almeida e Souza, 200, Mogi das Cruzes, SP, CEP 08780-911, Brazil.,Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX, USA
| | - Júlio César Claudino Dos Santos
- Laboratory of Neuroscience, Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, SP, Brazil
| | - Francisco Gonzalez-Lima
- Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX, USA
| | - Bruno Henrique Silva Araújo
- Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, SP, Brazil
| | - Rodrigo Álvaro Brandão Lopes-Martins
- Laboratory of Biophotonics and Experimental Therapeutics, Institute of Research and Development, University of Vale do Paraíba (UNIVAP), São José dos Campos, SP, Brazil
| | - Sérgio Gomes da Silva
- Núcleo de Pesquisas Tecnológicas, Universidade de Mogi das Cruzes, Av. Cândido Xavier de Almeida e Souza, 200, Mogi das Cruzes, SP, CEP 08780-911, Brazil. .,Centro Universitário UNIFAMINAS (UNIFAMINAS), Muriaé, MG, Brazil. .,Hospital do Câncer de Muriaé, Fundação Cristiano Varella (FCV), Muriaé, MG, Brazil.
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26
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Akbarzadeh A, Sasanpour P, Moghimi HR. LED Photo-polymerization, a Novel Strategy for Triggered Release Liposomes. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2020; 19:260-270. [PMID: 32922485 PMCID: PMC7462490 DOI: 10.22037/ijpr.2019.112366.13712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
LED light is used for many medical and cosmetic applications such as phototherapy and skin rejuvenation. Such physical methods can be combined with drug therapy, such as LED-responsive drug delivery system, the subject of present investigation. To perform this investigation, a nanoliposome composed of DPPC, DSPE-PEG2000, and DC8,9PC, was prepared as LED-sensitive systems. Calcein was loaded in the liposomes as a fluorescent probe for drug release studies. Different LED wavelengths (blue, green and red) were used for triggering release of calcein from nanoliposome. Indoor daylight, darkness, and sunlight were applied as controls. Results showed that liposomes do not release their cargo in darkness, but they released it in response to indoor daylight, sunlight and LEDs, with the blue light showing the highest effect. Results also showed that release of calcein was sensitive to wavelength. Our results reveal potential of LED-sensitive liposomes for medical and cosmetic applications and that such system can be combined with phototherapy. Such concomitant therapies can increase medical/cosmetic effects and decrease adverse reactions to phototherapy.
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Affiliation(s)
- Afsoon Akbarzadeh
- Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pezhman Sasanpour
- Department of Medical Physics and Engineering, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid R Moghimi
- Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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27
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Mitra S, Kaushik N, Moon IS, Choi EH, Kaushik NK. Utility of Reactive Species Generation in Plasma Medicine for Neuronal Development. Biomedicines 2020; 8:E348. [PMID: 32932745 PMCID: PMC7555638 DOI: 10.3390/biomedicines8090348] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 09/07/2020] [Accepted: 09/09/2020] [Indexed: 12/13/2022] Open
Abstract
Reactive oxygen species (ROS) are critical signaling molecules for neuronal physiology that stimulate growth and development and play vital roles in several pathways when in a balanced state, but they cause neurodegeneration when unbalanced. As ROS levels above a certain threshold cause the activation of the autophagy system, moderate levels of ROS can be used as treatment strategies. Currently, such treatments are used together with low-level laser or photodynamic therapies, photo-bio modulation, or infrared treatments, in different chronic diseases but not in the treatment of neurodegeneration. Recently, non-thermal plasma has been successfully used in biomedical applications and treatments, and beneficial effects such as differentiation, cell growth, and proliferation, stimulation of ROS based pathways have been observed. Besides the activation of a wide range of biological signaling pathways by generating ROS, plasma application can be an effective treatment in neuronal regeneration, as well as in neuronal diseases. In this review, we summarize the generation and role of ROS in neurons and provide critical insights into their potential benefits on neurons. We also discuss the underlying mechanisms of ROS on neuronal development. Regarding clinical applications, we focus on ROS-based neuronal growth and regeneration strategies and in the usage of non-thermal plasma in neuronal and CNS injury treatments.
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Affiliation(s)
- Sarmistha Mitra
- Plasma Bioscience Research Center/Applied Plasma Medicine Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Korea;
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea;
| | - Neha Kaushik
- Department of Biotechnology, University of Suwon, Hwaseong 18323, Korea;
| | - Il Soo Moon
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju 38066, Korea;
| | - Eun Ha Choi
- Plasma Bioscience Research Center/Applied Plasma Medicine Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Korea;
| | - Nagendra Kumar Kaushik
- Plasma Bioscience Research Center/Applied Plasma Medicine Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Korea;
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Chao LL, Barlow C, Karimpoor M, Lim L. Changes in Brain Function and Structure After Self-Administered Home Photobiomodulation Treatment in a Concussion Case. Front Neurol 2020; 11:952. [PMID: 33013635 PMCID: PMC7509409 DOI: 10.3389/fneur.2020.00952] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Traumatic brain injury (TBI) is a common neurological disorder among athletes. Although there are no widely accepted treatments for TBI, new investigational approaches, such as photobiomodulation (PBM), are being tested. PBM is a light therapy that uses red to near-infrared (NIR) light to stimulate, heal, and protect tissue that has been injured or is at risk of dying. Benefits following transcranial PBM treatments in animal models of acute TBI and a small number of chronic TBI patients have been reported. However, the human PBM TBI studies published to date have been based on behavioral assessments. This report describes changes in behavioral and neuroimaging measures after 8 weeks of PBM treatments. The subject was a 23-year professional hockey player with a history of concussions, presumed to have caused his symptoms of headaches, mild anxiety, and difficulty concentrating. He treated himself at home with commercially available, low-risk PBM devices that used light-emitting diodes (LEDs) to emit 810-nm light pulsing at 10 or 40 Hz delivered by an intranasal and four transcranial modules that targeted nodes of the default mode network (DMN) with a maximum power density of 100 mW/cm2. After 8 weeks of PBM treatments, increased brain volumes, improved functional connectivity, and increased cerebral perfusion and improvements on neuropsychological test scores were observed. Although this is a single, sport-related case with a history of concussions, these positive findings encourage replication studies that could provide further validation for this non-invasive, non-pharmacological modality as a viable treatment option for TBI.
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Affiliation(s)
- Linda L Chao
- Departments of Radiology & Biomedical Imaging and Psychiatry & Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States.,VA Advanced Imaging Research Center, San Francisco VA Health Care System, San Francisco, CA, United States
| | - Cody Barlow
- VA Advanced Imaging Research Center, San Francisco VA Health Care System, San Francisco, CA, United States
| | | | - Lew Lim
- Vielight Inc., Toronto, ON, Canada
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Li Y, Xu X, Liu X, Li B, Han Y, Zheng Y, Chen D, Yeung KWK, Cui Z, Li Z, Liang Y, Zhu S, Wang X, Wu S. Photoelectrons Mediating Angiogenesis and Immunotherapy through Heterojunction Film for Noninvasive Disinfection. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2020; 7:2000023. [PMID: 32999817 PMCID: PMC7507565 DOI: 10.1002/advs.202000023] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 05/31/2020] [Indexed: 05/23/2023]
Abstract
A light-inspired hydroxyapatite (Hap)/nitrogen-doped carbon dots (NCDs) modified graphene oxide (GO) heterojunction film is developed, which shows a promoted separation of interfacial electrons and holes and an inhibited recombination efficiency via hole depletion. The metabolism of bacteria on this film is significantly inhibited under light irradiation, due to the enhanced photocatalytic and photothermal effects. In addition, the electron transfer from the plasmonic membrane to the GO/NCD/Hap film further inhibits the adenosine triphosphate process of bacteria, thus leading to the synergetic antibacterial efficacy. Meanwhile, the electron transfer between film and cell membrane induces the Ca2+ flow after irradiation, which can promote the migration and proliferation of cells and alkaline phosphatase enhancement, thus favoring the tissue reconstruction. An in vivo test discloses that the vascular injury repair is achieved through the Ca2+-activated PLCγ1/ERK pathway, identified by the enhanced CD31 expression. Moreover, the increased CD4+/CD8+ lymphocytes are ameliorative by activating the PI3K/P-AKT pathway. Consequently, the electron transfer boosts the synergic photodynamic and photothermal therapeutic effects for bacterial infection by Ca2+ flow for immunotherapy. This mild phototherapy approach with GO/NCDs/Hap, which can simultaneously repair injured vessels and relieve inflammation reactions, will increase the clinical application of noninvasive phototherapy in the near future.
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Affiliation(s)
- Yuan Li
- The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaSchool of Materials Science and EngineeringTianjin UniversityTianjin300072China
| | - Xiaomo Xu
- Hubei Key Laboratory of Polymer MaterialsMinistry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional MaterialsSchool of Materials Science and EngineeringHubei UniversityWuhan430062China
| | - Xiangmei Liu
- Hubei Key Laboratory of Polymer MaterialsMinistry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional MaterialsSchool of Materials Science and EngineeringHubei UniversityWuhan430062China
| | - Bo Li
- State Key Laboratory for Mechanical Behavior of MaterialsSchool of Materials Science and EngineeringXi'an Jiaotong UniversityXi'anShaanxi710049China
| | - Yong Han
- State Key Laboratory for Mechanical Behavior of MaterialsSchool of Materials Science and EngineeringXi'an Jiaotong UniversityXi'anShaanxi710049China
| | - Yufeng Zheng
- State Key Laboratory for Turbulence and Complex SystemDepartment of Materials Science and EngineeringCollege of EngineeringPeking UniversityBeijing100871China
| | - Da‐fu Chen
- Laboratory Bone Tissue EngineeringBeijing Research Institute Orthopaedics and TraumatologyBeijing JiShuiTan HospitalBeijing100035P. R. China
| | - Kelvin Wai Kwok Yeung
- Department of Orthopaedics and TraumatologyLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong999077China
| | - Zhenduo Cui
- The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaSchool of Materials Science and EngineeringTianjin UniversityTianjin300072China
| | - Zhaoyang Li
- The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaSchool of Materials Science and EngineeringTianjin UniversityTianjin300072China
| | - Yanqin Liang
- The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaSchool of Materials Science and EngineeringTianjin UniversityTianjin300072China
| | - Shengli Zhu
- The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaSchool of Materials Science and EngineeringTianjin UniversityTianjin300072China
| | - Xianbao Wang
- Hubei Key Laboratory of Polymer MaterialsMinistry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional MaterialsSchool of Materials Science and EngineeringHubei UniversityWuhan430062China
| | - Shuilin Wu
- The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of ChinaSchool of Materials Science and EngineeringTianjin UniversityTianjin300072China
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Sasso LL, de Souza LG, Girasol CE, Marcolino AM, de Jesus Guirro RR, Barbosa RI. Photobiomodulation in Sciatic Nerve Crush Injuries in Rodents: A Systematic Review of the Literature and Perspectives for Clinical Treatment. J Lasers Med Sci 2020; 11:332-344. [PMID: 32802295 DOI: 10.34172/jlms.2020.54] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Objective : The aim of the study was to perform a literature review to analyze the effect of photobiomodulation in experimental studies on peripheral nerve regeneration after sciatic nerve crush injury in rodents. Methods: A bibliographic search was performed in the electronic databases, including MEDLINE (PubMed), SCOPUS, and SciELO, from 2008 to 2018. Results: A total of 1912 articles were identified in the search, and only 19 fulfilled all the inclusion criteria. Along with the parameters most found in the manuscripts, the most used wavelengths were 660 nm and 830 nm, power of 30 and 40 mW, and energy density of 4 and 10 J/cm2 . For total energy throughout the intervention period, the lowest energy found with positive effects was 0.70 J, and the highest 1.141 J. Seventeen studies reported positive effects on nerve regeneration. The variables selected to analyze the effect were: Sciatic Functional Index (SFI), Static Sciatic Index (SSI), morphometric, morphological, histological, zymographic, electrophysiological, resistance mechanics and range of motion (ROM). The variety of parameters used in the studies demonstrated that there is yet no pre-determined protocol for treating peripheral nerve regeneration. Only two studies by different authors used the same power, energy density, beam area, and power density. Conclusion: It was concluded that the therapeutic window of the photobiomodulation presents a high variability of parameters with the wavelength (632.8 to 940 nm), power (5 to 170 mW) and energy density (3 to 280 J /cm2 ), promoting nerve regeneration through the expression of cytokines and growth factors that aid in modulating the inflammatory process, improving morphological aspects, restoring the functionality to the animals in a brief period.
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Affiliation(s)
- Letícia Lemes Sasso
- Department of Health Sciences, Federal University of Santa Catarina/UFSC - Araranguá, Brazil
| | - Luana Gabriel de Souza
- Postgraduate Program in Rehabilitation Sciences, Federal University of Santa Catarina / UFSC - Araranguá, Brazil
| | - Carlos Eduardo Girasol
- Postgraduate Program in Rehabilitation and Functional Performance, University of São Paulo/USP - Ribeirão Preto, Brazil
| | - Alexandre Márcio Marcolino
- Postgraduate Program in Rehabilitation Sciences, Federal University of Santa Catarina / UFSC - Araranguá, Brazil
| | | | - Rafael Inácio Barbosa
- Postgraduate Program in Rehabilitation Sciences, Federal University of Santa Catarina / UFSC - Araranguá, Brazil.,Postgraduate Program in Rehabilitation and Functional Performance, University of São Paulo/USP - Ribeirão Preto, Brazil
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31
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Henderson TA, van Lierop MJ, McLean M, Uszler JM, Thornton JF, Siow YH, Pavel DG, Cardaci J, Cohen P. Functional Neuroimaging in Psychiatry-Aiding in Diagnosis and Guiding Treatment. What the American Psychiatric Association Does Not Know. Front Psychiatry 2020; 11:276. [PMID: 32351416 PMCID: PMC7176045 DOI: 10.3389/fpsyt.2020.00276] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 03/23/2020] [Indexed: 12/12/2022] Open
Abstract
While early efforts in psychiatry were focused on uncovering the neurobiological basis of psychiatric symptoms, they made little progress due to limited ability to observe the living brain. Today, we know a great deal about the workings of the brain; yet, none of this neurobiological awareness has translated into the practice of psychiatry. The categorical system which dominates psychiatric diagnosis and thinking fails to match up to the real world of genetics, sophisticated psychological testing, and neuroimaging. Nevertheless, the American Psychiatric Association (APA) recently published a position paper stating that neuroimaging provided no benefit to the diagnosis and treatment of psychiatric disorders. Using the diagnosis of depression as a model, we illustrate how setting aside the unrealistic expectation of a pathognomonic "fingerprint" for categorical diagnoses, we can avoid missing the biological and, therefore, treatable contributors to psychopathology which can and are visualized using functional neuroimaging. Infection, toxicity, inflammation, gut-brain dysregulation, and traumatic brain injury can all induce psychiatric manifestations which masquerade as depression and other psychiatric disorders. We review these and provide illustrative clinical examples. We further describe situations for which single photon emission computed tomography (SPECT) and positron emission tomography (PET) functional neuroimaging already meet or exceed the criteria set forth by the APA to define a neuroimaging biomarker, including the differential diagnosis of Alzheimer's disease and other dementias, the differential diagnosis of ADHD, and the evaluation of traumatic brain injury. The limitations, both real and perceived, of SPECT and PET functional neuroimaging in the field of psychiatry are also elaborated. An important overarching concept for diagnostic imaging in all its forms, including functional neuroimaging, is that imaging allows a clinician to eliminate possibilities, narrow the differential diagnosis, and tailor the treatment plan. This progression is central to any medical diagnostic process.
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Affiliation(s)
- Theodore A. Henderson
- The Synaptic Space, Inc., Denver, CO, United States
- Neuro-Luminance, Inc., Denver, CO, United States
- Dr. Theodore Henderson, Inc., Denver, CO, United States
- International Society of Applied Neuroimaging, Denver, CO, United States
| | - Muriel J. van Lierop
- International Society of Applied Neuroimaging, Denver, CO, United States
- Private Practice, Toronto, ON, Canada
| | - Mary McLean
- International Society of Applied Neuroimaging, Denver, CO, United States
- Private Practice, Toronto, ON, Canada
| | - John Michael Uszler
- International Society of Applied Neuroimaging, Denver, CO, United States
- Nuclear Medicine, Providence St. John's Health Center, Santa Monica, CA, United States
- Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, United States
| | - John F. Thornton
- International Society of Applied Neuroimaging, Denver, CO, United States
- Rossiter-Thornton Associates, Toronto, ON, Canada
| | - Yin-Hui Siow
- International Society of Applied Neuroimaging, Denver, CO, United States
- Nuclear Medicine, Southlake Regional Health Centre, Newmarket, ON, Canada
| | - Dan G. Pavel
- International Society of Applied Neuroimaging, Denver, CO, United States
- PathFinder Brain SPECT, Deerfield, IL, United States
| | - Joe Cardaci
- International Society of Applied Neuroimaging, Denver, CO, United States
- Fremantle-School of Medicine, University of Notre Dame, Fremantle, WA, Australia
- Diagnostic Nuclear Medicine, Hollywood Private Hospital, Nedlands, WA, Australia
- Consultant Physician, Perth, WA, Australia
| | - Phil Cohen
- International Society of Applied Neuroimaging, Denver, CO, United States
- Nuclear Medicine, Lions Gate Hospital, Vancouver, BC, Canada
- Radiology, University of British Columbia, Vancouver, BC, Canada
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Rosso MPDO, Buchaim DV, Pomini KT, Coletta BBD, Reis CHB, Pilon JPG, Duarte Júnior G, Buchaim RL. Photobiomodulation Therapy (PBMT) Applied in Bone Reconstructive Surgery Using Bovine Bone Grafts: A Systematic Review. MATERIALS (BASEL, SWITZERLAND) 2019; 12:4051. [PMID: 31817369 PMCID: PMC6947623 DOI: 10.3390/ma12244051] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/22/2019] [Accepted: 11/29/2019] [Indexed: 02/07/2023]
Abstract
The use of low-level laser therapy (LLLT) with biomodulatory effects on biological tissues, currently called photobiomodulation therapy (PBMT), assists in healing and reduces inflammation. The application of biomaterials has emerged in bone reconstructive surgery, especially the use of bovine bone due to its biocompatibility. Due to the many benefits related to the use of PBMT and bovine bones, the aim of this research was to review the literature to verify the relationship between PBMT and the application of bovine bone in bone reconstruction surgeries. We chose the PubMed/MEDLINE, Web of Science, and Scopus databases for the search by matching the keywords: "Bovine bone AND low-level laser therapy", "Bovine bone AND photobiomodulation therapy", "Xenograft AND low-level laser therapy", and "Xenograft AND photobiomodulation therapy". The initial search of the three databases retrieved 240 articles, 18 of which met all inclusion criteria. In the studies concerning animals (17 in total), there was evidence of PBMT assisting in biomaterial-related conduction, formation of new bone, bone healing, immunomarker expression, increasing collagen fibers, and local inflammation reduction. However, the results disagreed with regard to the resorption of biomaterial particles. The only human study showed that PBMT with bovine bone was effective for periodontal regeneration. It was concluded that PBMT assists the process in bone reconstruction when associated with bovine bone, despite divergences between applied protocols.
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Affiliation(s)
- Marcelie Priscila de Oliveira Rosso
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisolla, 9-75-Vila Universitaria, Bauru, SP 17012-901, Brazil; (M.P.d.O.R.); (K.T.P.); (B.B.D.C.)
| | - Daniela Vieira Buchaim
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília, SP 17525–902, Brazil; (D.V.B.); (C.H.B.R.); (J.P.G.P.); (G.D.J.)
- Medical School, University Center of Adamantina (UniFAI), Nove de Julho Street, 730-Centro, Adamantina, SP 17800-000, Brazil
| | - Karina Torres Pomini
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisolla, 9-75-Vila Universitaria, Bauru, SP 17012-901, Brazil; (M.P.d.O.R.); (K.T.P.); (B.B.D.C.)
| | - Bruna Botteon Della Coletta
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisolla, 9-75-Vila Universitaria, Bauru, SP 17012-901, Brazil; (M.P.d.O.R.); (K.T.P.); (B.B.D.C.)
| | - Carlos Henrique Bertoni Reis
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília, SP 17525–902, Brazil; (D.V.B.); (C.H.B.R.); (J.P.G.P.); (G.D.J.)
| | - João Paulo Galletti Pilon
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília, SP 17525–902, Brazil; (D.V.B.); (C.H.B.R.); (J.P.G.P.); (G.D.J.)
| | - Getúlio Duarte Júnior
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília, SP 17525–902, Brazil; (D.V.B.); (C.H.B.R.); (J.P.G.P.); (G.D.J.)
| | - Rogério Leone Buchaim
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisolla, 9-75-Vila Universitaria, Bauru, SP 17012-901, Brazil; (M.P.d.O.R.); (K.T.P.); (B.B.D.C.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenue Hygino Muzzy Filho, 1001, Marília, SP 17525–902, Brazil; (D.V.B.); (C.H.B.R.); (J.P.G.P.); (G.D.J.)
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Askalsky P, Iosifescu DV. Transcranial Photobiomodulation For The Management Of Depression: Current Perspectives. Neuropsychiatr Dis Treat 2019; 15:3255-3272. [PMID: 31819453 PMCID: PMC6878920 DOI: 10.2147/ndt.s188906] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 10/26/2019] [Indexed: 12/16/2022] Open
Abstract
Major depressive disorder (MDD) is a prevalent condition associated with high rates of disability, as well as suicidal ideation and behavior. Current treatments for MDD have significant limitations in efficacy and side effect burden. FDA-approved devices for MDD are burdensome (due to repeated in-office procedures) and are most suitable for severely ill subjects. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and easy to use. In this paper, we review a novel neuromodulation strategy, transcranial photobiomodulation (t-PBM) with near-infrared light (NIR). The scope of our review includes the known biological mechanisms of t-PBM, as well as its efficacy in animal models of depression and in patients with MDD. Theoretically, t-PBM penetrates into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow. Animal and human studies, using a variety of t-PBM settings and experimental models, suggest that t-PBM may have significant efficacy and good tolerability in MDD. In aggregate, these data support the need for large confirmatory studies for t-PBM as a novel, likely safe, and easy-to-administer antidepressant treatment.
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Affiliation(s)
- Paula Askalsky
- Department of Psychiatry, NYU Langone School of Medicine, New York, NY, USA
| | - Dan V Iosifescu
- Department of Psychiatry, NYU Langone School of Medicine, New York, NY, USA
- Clinical Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
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Maiello M, Losiewicz OM, Bui E, Spera V, Hamblin MR, Marques L, Cassano P. Transcranial Photobiomodulation with Near-Infrared Light for Generalized Anxiety Disorder: A Pilot Study. Photobiomodul Photomed Laser Surg 2019; 37:644-650. [PMID: 31647775 PMCID: PMC6818480 DOI: 10.1089/photob.2019.4677] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 07/23/2019] [Indexed: 01/09/2023] Open
Abstract
Objective: Our aim was to test the anxiolytic effect of transcranial photobiomodulation (t-PBM) with near-infrared light (NIR) in subjects suffering from generalized anxiety disorder (GAD). Background: t-PBM with NIR is an experimental, noninvasive treatment for mood and anxiety disorders. Preliminary evidence indicates a potential anxiolytic effect of transcranial NIR. Methods: Fifteen subjects suffering from GAD were recruited in an open-label 8-week study. Each participant self-administered t-PBM daily, for 20 min (continuous wave; 830 nm peak wavelength; average irradiance 30 mW/cm2; average fluence 36 J/cm2; total energy delivered per session 2.9 kJ: total output power 2.4 W) broadly on the forehead (total area 80 cm2) with an LED-cluster headband (Cerebral Sciences). Outcome measures were the reduction in total scores of the Hamilton Anxiety Scale (SIGH-A), the Clinical Global Impressions-Severity (CGI-S) subscale and the Pittsburgh Sleep Quality Index (PSQI) subscales from baseline to last observation carried forward. Results: Of the 15 recruited subjects (mean age 30 ± 14 years; 67% women), 12 (80%) completed the open trial. Results show a significant reduction in the total scores of SIGH-A (from 17.27 ± 4.89 to 8.47 ± 4.87; p < 0.001; Cohen's d effect size = 1.47), in the CGI-S subscale (from 4.53 ± 0.52 to 2.87 ± 0.83; p < 0.001; Cohen's d effect size = 2.04), as well as significant improvements in sleep at the PSQI. t-PBM was well tolerated with no serious adverse events. Conclusions: Based on our pilot study, t-PBM with NIR is a promising alternative treatment for GAD. Larger, randomized, double-blind, sham-controlled studies are needed.
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Affiliation(s)
- Marco Maiello
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Olivia M. Losiewicz
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
| | - Eric Bui
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
| | - Vincenza Spera
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Michael R. Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
- Department of Dermatology, Harvard Medical School, Boston, Massachusetts
| | - Luana Marques
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
| | - Paolo Cassano
- Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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35
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Carneiro AMC, Poiani GC, Zaninnoto AL, Lazo Osorio R, Oliveira MDL, Paiva WS, Zângaro RA. Transcranial Photobiomodulation Therapy in the Cognitive Rehabilitation of Patients with Cranioencephalic Trauma. Photobiomodul Photomed Laser Surg 2019; 37:657-666. [PMID: 31647777 PMCID: PMC6818475 DOI: 10.1089/photob.2019.4683] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 08/06/2019] [Indexed: 12/13/2022] Open
Abstract
Objective: This research evaluated the hemodynamic conditions before and after the transcranial photobiomodulation therapy (PBMT) and investigated neurocognitive changes before and after treatment. Background: Traumatic brain injury (TBI) is the major cause of morbidity and mortality among individuals 21-60 years old and causes ∼500,000 people to be hospitalized in Brazil annually. Some survivors develop an irreversible decrease in neurological function, and the mortality rate is as high as 70% in severe cases. PBMT is an alternative to treat secondary injuries due to TBI. Methods: This multidisciplinary clinical study was carried out on 10 chronic adult patients with severe TBI, who were treated with PBMT with an optical device containing 13 sets of 4 light emitting diodes, and underwent hemodynamic transcranial Doppler and neuropsychological evaluation at three different times: pre-PBMT, post-PBMT (after a week), and late-PBMT, which occurred 3 months after the last session. The patients received PBMTs three times a week, for 6 weeks. PBMTs were performed for 18 sessions for 6 weeks and 30 min per session. Results: The results found an alteration in the cerebral blood flow (CBF) as well as a consequent increase of the cerebral oxygenation that helped to improve the cerebral function. Conclusions: The PBMT contributed to increased CBF, evidenced mainly by the increased left peak systolic velocity, which consequently increased the hemodynamic response after the PBMT and impacts on the peripheral cerebral perfusion contributing to improved cerebral function.
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Affiliation(s)
- Ana Maria Costa Carneiro
- Stricto Sensu Program Master and Doctorate in Biomedical Engineering, Anhembi Morumbi University, São José dos Campos, São Paulo, Brasil
| | - Guilherme Cruz Poiani
- Division of Neurosurgery, Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP), São Paulo, Brasil
| | - Ana Luiza Zaninnoto
- Speech and Feeding Disorders Lab, MGH Institute of Health Professional, Marion, Ohio
| | - Rodrigo Lazo Osorio
- Stricto Sensu Program Master and Doctorate in Biomedical Engineering, Anhembi Morumbi University, São José dos Campos, São Paulo, Brasil
- Center for Innovation Technology and Education (CITÉ), Anhembi Morumbi University, São José dos Campos, São Paulo, Brasil
| | - Marcelo de Lima Oliveira
- Division of Neurosurgery, Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP), São Paulo, Brasil
| | - Wellingson Silva Paiva
- Division of Neurosurgery, Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP), São Paulo, Brasil
| | - Renato Amaro Zângaro
- Stricto Sensu Program Master and Doctorate in Biomedical Engineering, Anhembi Morumbi University, São José dos Campos, São Paulo, Brasil
- Center for Innovation Technology and Education (CITÉ), Anhembi Morumbi University, São José dos Campos, São Paulo, Brasil
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Zinchenko E, Navolokin N, Shirokov A, Khlebtsov B, Dubrovsky A, Saranceva E, Abdurashitov A, Khorovodov A, Terskov A, Mamedova A, Klimova M, Agranovich I, Martinov D, Tuchin V, Semyachkina-Glushkovskaya O, Kurts J. Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for non-pharmacologic therapy of Alzheimer's disease. BIOMEDICAL OPTICS EXPRESS 2019; 10:4003-4017. [PMID: 0 PMCID: PMC6701516 DOI: 10.1364/boe.10.004003] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/07/2019] [Accepted: 07/08/2019] [Indexed: 05/03/2023]
Abstract
In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm2) on clearance of beta-amyloid (Aβ) from the mouse brain. The immunohistochemical and confocal data clearly demonstrate the significant reduction of deposition of Aβ plaques in mice after tPBM vs. untreated animals. The behavior tests showed that tPBM improved the cognitive, memory and neurological status of mice with Alzheimer's disease (AD). Using of our original method based on optical coherence tomography (OCT) analysis of clearance of gold nanorods (GNRs) from the brain, we proposed possible mechanism underlying tPBM-stimulating effects on clearance of Aβ via the lymphatic system of the brain and the neck. These results open breakthrough strategies for a non-pharmacological therapy of Alzheimer's disease and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying Alzheimer's disease.
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Affiliation(s)
| | - Nikita Navolokin
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
- Saratov State Medical University, Saratov 410012, Russia
| | - Alexander Shirokov
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
- Saratov State Medical University, Saratov 410012, Russia
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Entusiastov Str. 13, Saratov 410049, Russia
| | - Boris Khlebtsov
- Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Entusiastov Str. 13, Saratov 410049, Russia
| | | | - Elena Saranceva
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
| | - Arkady Abdurashitov
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
- Tomsk State University, Laboratory of Biophotonics, 36 Lenin's Ave., Tomsk 634050, Russian Federation
| | | | - Andrey Terskov
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
| | - Aysel Mamedova
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
| | - Maria Klimova
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
| | - Ilana Agranovich
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
| | - Dmitry Martinov
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
| | - Valery Tuchin
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
- Tomsk State University, Laboratory of Biophotonics, 36 Lenin's Ave., Tomsk 634050, Russian Federation
- Institute of Precision Mechanics and Control of the Russian Academy of Sciences, 24 Rabochaya Str., Saratov 410028, Russian Federation
| | | | - Jurgen Kurts
- Saratov State University, Astrakhanskaya Str. 83, Saratov 410012, Russia
- Physics Department, Humboldt University, Newtonstrasse 15, 12489 Berlin, Germany
- Potsdam Institute for Climate Impact Research, Telegrafenberg A31, 14473 Potsdam, Germany
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Bhattacharya M, Dutta A. Computational Modeling of the Photon Transport, Tissue Heating, and Cytochrome C Oxidase Absorption during Transcranial Near-Infrared Stimulation. Brain Sci 2019; 9:brainsci9080179. [PMID: 31357574 PMCID: PMC6721367 DOI: 10.3390/brainsci9080179] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 07/15/2019] [Accepted: 07/23/2019] [Indexed: 12/16/2022] Open
Abstract
Transcranial near-infrared stimulation (tNIRS) has been proposed as a tool to modulate cortical excitability. However, the underlying mechanisms are not clear where the heating effects on the brain tissue needs investigation due to increased near-infrared (NIR) absorption by water and fat. Moreover, the risk of localized heating of tissues (including the skin) during optical stimulation of the brain tissue is a concern. The challenge in estimating localized tissue heating is due to the light interaction with the tissues' constituents, which is dependent on the combination ratio of the scattering and absorption properties of the constituent. Here, apart from tissue heating that can modulate the cortical excitability ("photothermal effects"); the other mechanism reported in the literature is the stimulation of the mitochondria in the cells which are active in the adenosine triphosphate (ATP) synthesis. In the mitochondrial respiratory chain, Complex IV, also known as the cytochrome c oxidase (CCO), is the unit four with three copper atoms. The absorption peaks of CCO are in the visible (420-450 nm and 600-700 nm) and the near-infrared (760-980 nm) spectral regions, which have been shown to be promising for low-level light therapy (LLLT), also known as "photobiomodulation". While much higher CCO absorption peaks in the visible spectrum can be used for the photobiomodulation of the skin, 810 nm has been proposed for the non-invasive brain stimulation (using tNIRS) due to the optical window in the NIR spectral region. In this article, we applied a computational approach to delineate the "photothermal effects" from the "photobiomodulation", i.e., to estimate the amount of light absorbed individually by each chromophore in the brain tissue (with constant scattering) and the related tissue heating. Photon migration simulations were performed for motor cortex tNIRS based on a prior work that used a 500 mW cm - 2 light source placed on the scalp. We simulated photon migration at 630 nm and 700 nm (red spectral region) and 810 nm (near-infrared spectral region). We found a temperature increase in the scalp below 0.25 °C and a minimal temperature increase in the gray matter less than 0.04 °C at 810 nm. Similar heating was found for 630 nm and 700 nm used for LLLT, so photothermal effects are postulated to be unlikely in the brain tissue.
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Affiliation(s)
- Mahasweta Bhattacharya
- Department of Biomedical Engineering, University at Buffalo SUNY, Buffalo, NY 14260, USA.
| | - Anirban Dutta
- Department of Biomedical Engineering, University at Buffalo SUNY, Buffalo, NY 14260, USA
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Facchin F, Canaider S, Tassinari R, Zannini C, Bianconi E, Taglioli V, Olivi E, Cavallini C, Tausel M, Ventura C. Physical energies to the rescue of damaged tissues. World J Stem Cells 2019; 11:297-321. [PMID: 31293714 PMCID: PMC6600852 DOI: 10.4252/wjsc.v11.i6.297] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 04/24/2019] [Accepted: 05/29/2019] [Indexed: 02/06/2023] Open
Abstract
Rhythmic oscillatory patterns sustain cellular dynamics, driving the concerted action of regulatory molecules, microtubules, and molecular motors. We describe cellular microtubules as oscillators capable of synchronization and swarming, generating mechanical and electric patterns that impact biomolecular recognition. We consider the biological relevance of seeing the inside of cells populated by a network of molecules that behave as bioelectronic circuits and chromophores. We discuss the novel perspectives disclosed by mechanobiology, bioelectromagnetism, and photobiomodulation, both in term of fundamental basic science and in light of the biomedical implication of using physical energies to govern (stem) cell fate. We focus on the feasibility of exploiting atomic force microscopy and hyperspectral imaging to detect signatures of nanomotions and electromagnetic radiation (light), respectively, generated by the stem cells across the specification of their multilineage repertoire. The chance is reported of using these signatures and the diffusive features of physical waves to direct specifically the differentiation program of stem cells in situ, where they already are resident in all the tissues of the human body. We discuss how this strategy may pave the way to a regenerative and precision medicine without the needs for (stem) cell or tissue transplantation. We describe a novel paradigm based upon boosting our inherent ability for self-healing.
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Affiliation(s)
- Federica Facchin
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Silvia Canaider
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Riccardo Tassinari
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Chiara Zannini
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Eva Bianconi
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Valentina Taglioli
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Elena Olivi
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Claudia Cavallini
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | | | - Carlo Ventura
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy.
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Salehpour F, Farajdokht F, Mahmoudi J, Erfani M, Farhoudi M, Karimi P, Rasta SH, Sadigh-Eteghad S, Hamblin MR, Gjedde A. Photobiomodulation and Coenzyme Q 10 Treatments Attenuate Cognitive Impairment Associated With Model of Transient Global Brain Ischemia in Artificially Aged Mice. Front Cell Neurosci 2019; 13:74. [PMID: 30983970 PMCID: PMC6434313 DOI: 10.3389/fncel.2019.00074] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 02/14/2019] [Indexed: 01/11/2023] Open
Abstract
Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q10 (CoQ10) administration are known to stimulate mitochondrial electron transport that potentially may reverse the effects of cerebral ischemia in aged animals. We tested the hypothesis that the effects of PBM and CoQ10, separately or in combination, improve cognition in a mouse model of transient cerebral ischemia superimposed on a model of aging. We modeled aging by 6-week administration of D-galactose (500 mg/kg subcutaneous) to mice. We subsequently induced transient cerebral ischemia by bilateral occlusion of the common carotid artery (BCCAO). We treated the mice with PBM (810 nm transcranial laser) or CoQ10 (500 mg/kg by gavage), or both, for 2 weeks after surgery. We assessed cognitive function by the Barnes and Lashley III mazes and the What-Where-Which (WWWhich) task. PBM or CoQ10, and both, improved spatial and episodic memory in the mice. Separately and together, the treatments lowered reactive oxygen species and raised ATP and general mitochondrial activity as well as biomarkers of mitochondrial biogenesis, including SIRT1, PGC-1α, NRF1, and TFAM. Neuroinflammatory responsiveness declined, as indicated by decreased iNOS, TNF-α, and IL-1β levels with the PBM and CoQ10 treatments. Collectively, the findings of this preclinical study imply that the procognitive effects of NIR PBM and CoQ10 treatments, separately or in combination, are beneficial in a model of transient global brain ischemia superimposed on a model of aging in mice.
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Affiliation(s)
- Farzad Salehpour
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran
- ProNeuroLIGHT LLC, Phoenix, AZ, United States
| | - Fereshteh Farajdokht
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Mahmoudi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Marjan Erfani
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Higher Educational Institute of Rab-Rashid, Tabriz, Iran
| | - Mehdi Farhoudi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Pouran Karimi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Hossein Rasta
- Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Bioengineering, Tabriz University of Medical Sciences, Tabriz, Iran
- School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Saeed Sadigh-Eteghad
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Michael R. Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, United States
- Department of Dermatology, Harvard Medical School, Boston, MA, United States
- Harvard-MIT Health Sciences and Technology, Cambridge, MA, United States
| | - Albert Gjedde
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Departments of Clinical Research and Nuclear Medicine, Odense University Hospital, University of Southern Denmark, Odense, Denmark
- Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark
- Department of Neurology & Neurosurgery, McGill University, Montreal, QC, Canada
- Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States
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de Jesus Fonseca EG, Pedroso A, Neuls D, Barbosa D, Cidral-Filho FJ, Salgado ASI, Dubiela A, Carraro E, Kerppers II. Study of transcranial therapy 904 nm in experimental model of stroke. Lasers Med Sci 2019; 34:1619-1625. [PMID: 30826952 DOI: 10.1007/s10103-019-02758-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 02/20/2019] [Indexed: 12/12/2022]
Abstract
Cerebrovascular accidents (CVAs), commonly known as strokes, can damage the brain through vascular injuries caused by either blood vessel blockages (ischemic stroke) or ruptures (hemorrhagic stroke) which disrupt regular brain blood supply and can cause severe damage to the individual. The objective of the present study was to evaluate the effects of photobiomodulation with a light-emitting diode (LED) device (904 nm, 110 mW, 7 J/cm2) on neurogenesis, muscle resistance, and motor behavior in animals submitted to an experimental model of hemiplegia. The sample consisted of 30 Wistar rats, divided into two groups: control group (GC) and 904-nm LED-treated group (TG). All animals underwent stereotactic surgery for electrode implant and subsequent electrolytic injury to induce an ischemic stroke. TG was subjected to daily LED irradiation (904 nm, 110 mW, 7 J/cm2) for 63 s. Suspension test results indicate an improvement of TG muscle resistance when compared with baseline evaluation (BLT); a reduction in open-field freezing time and the number of fecal bolus pellets suggest diminished anxiety induced by 904-nm LED treatment on treatment days 7 and 21 (TG7 and TG21) compared with the baseline results; and lastly, histological analysis showed important signs of neurogenesis in TG in comparison to CG, especially on treatment days 7 and 21 (TG7 and TG21). In conclusion, the present study suggests that 904-nm LED irradiation may beneficially affect neurogenesis, muscle resistance, and animal motor behavior following ischemic CVA.
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Affiliation(s)
| | - Ariele Pedroso
- Laboratory of Neuroanatomy and Neurophysiology, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil
| | - Débora Neuls
- Laboratory of Neuroanatomy and Neurophysiology, Universidade Estadual do Centro-Oeste, Guarapuava, PR, Brazil
| | - Danilo Barbosa
- Department of Physical Therapy, Functional Neurology Discipline, Universidade Estadual do Centro Oeste, Guarapuava, PR, Brazil
| | - Francisco José Cidral-Filho
- Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil
| | | | - Angela Dubiela
- Laboratório de Neuroanatomia e Neurofisiologia, Universidade Estadual do Centro-Oeste, Simeão Camargo Varela de Sá, 03, Guarapuava, Paraná, 88040-080, Brazil
| | - Emerson Carraro
- Laboratório de Imunologia, virologia e Biologia Molecular, Universidade Estadual do Centro-Oeste, Guarapuava, Paraná, Brazil
| | - Ivo Ilvan Kerppers
- Laboratório de Neuroanatomia e Neurofisiologia, Universidade Estadual do Centro-Oeste, Simeão Camargo Varela de Sá, 03, Guarapuava, Paraná, 88040-080, Brazil.
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Yao X, Liu C, Feng D, Yin J, Chen G. Transcranial Near-infrared Laser Therapy in Improving Cognitive Recovery of Function Following Traumatic Brain Injury. Curr Neuropharmacol 2018; 16:1320-1326. [PMID: 29564977 PMCID: PMC6251043 DOI: 10.2174/1570159x16666180321100439] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Revised: 07/25/2017] [Accepted: 02/28/2018] [Indexed: 11/23/2022] Open
Abstract
Abstract: Traumatic brain injury (TBI) has turned into a major health and socioeconomic problem affecting young people and military personnel. Numerous TBI patients experienced the sequela of brain injury called cognitive impairment, which re-duced functions in attention, working memory, motivation, and execution. In recent years, transcranial near-infrared laser therapy (tNiRLT) as a possible therapy has been gradually applied in treating cognitive impairment post-TBI. In the present review, the biological mechanisms of transcranial tNiRLT for TBI are synthesized mainly based on the photonic impact of chronic mild TBI. Various exciting molecular events possibly occur during the procedure, such as stimulation of ATP pro-duction, regional cerebral blood flow, acupoint, neurogenesis and synaptogenesis, as well as a reduction in anti-inflammatory effect. Some animal experiments and clinical studies of tNiRLT for TBI are outlined. Several labs have displayed that tNiRLT is effective not only in improving neurological functions but also in increasing memory and learning capacity in ro-dent animals’ model of TBI. In a 2 patients case report and a 11-case series, cognitive functions were ameliorated. Efficacy on cognitive and emotional effects was also observed in a double-blind, controlled clinical study. Several Randomized, paral-lel, double blind, sham-controlled trials are underway, aiming to evaluate the efficacy of tLED on cognitive functions and neuropsychiatric status in participants post-TBI. Therefore, tNiRLT is a promising method applied to cognitive impairment following TBI.
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Affiliation(s)
- Xiyang Yao
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China
| | - Chenglin Liu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China
| | - Dongxia Feng
- Scott & White Clinic-Temple, 2401 S.31st Street, Temple, TX76508, United States
| | - Jun Yin
- Department of Neurosurgery, Taixing Chinese Medicine Hospital, Taixing 225400, China
| | - Gang Chen
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China
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Papacharalambous M, Karvounis G, Kenanakis G, Gupta A, Rubinsky B. The Effect of Textiles Impregnated with Particles of High Emissivity in the Far Infrared, on the Temperature of the Cold Hand. J Biomech Eng 2018; 141:2716676. [PMID: 30458507 DOI: 10.1115/1.4042044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Indexed: 11/08/2022]
Abstract
In engineering and medicine, there is a growing interest in using textiles made of composites with enhanced thermal properties. One such type of textile is fabric impregnated with ceramics and mineral particles. This material has high emissivity in the infrared range and may have therapeutic benefits for treatments of diseases, like Raynaud's syndrome. While there is significant clinical and commercial interest, there is an evident lack of fundamental studies on the heat transfer aspects of these fabrics. The goal of this technical brief is to presents results from a fundamental study examining the thermal effects of fabric with ceramics and minerals (produced by Nanobionic Inc.) on the temperatures of the hands. With a confidence level of 90%, the results show that the textile with ceramics and minerals has an enhanced thermal effect on warming a cold hand in comparison to a placebo fabric without ceramics or minerals. Much more research is needed to increase the level of confidence and develop a fundamental understanding of the mechanism.
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Affiliation(s)
- Michael Papacharalambous
- Chief of Internal Medicine, Orthobiotiki Medical Center, 3-5 Sorou, Marousi, 15125, Athens, Greece
| | - Georgia Karvounis
- Orthobiotiki Medical Center, 3-5 Sorou, Marousi, 15125, Athens, Greece
| | - George Kenanakis
- Foundation for Research & Technology - Hellas (FORTH), Institute of Electronic Structure and Laser (IESL), N. Plastira 100, Vasilika Vouton, Heraklion, Crete, GR - 700 13, Greece
| | - Anshal Gupta
- Department of Mechanical Engineering, University of California Berkeley, Berkeley CA 94720 USA
| | - Boris Rubinsky
- Fellow ASME, Department of Mechanical Engineering, University of California Berkeley, Berkeley CA 94720 USA
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Near-infrared photobiomodulation combined with coenzyme Q 10 for depression in a mouse model of restraint stress: reduction in oxidative stress, neuroinflammation, and apoptosis. Brain Res Bull 2018; 144:213-222. [PMID: 30385146 DOI: 10.1016/j.brainresbull.2018.10.010] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 10/18/2018] [Accepted: 10/25/2018] [Indexed: 12/19/2022]
Abstract
This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q10 (CoQ10) on depressive-like behavior, cerebral oxidative stress, inflammation, and apoptosis markers in mice. To induce a depressive-like model, mice were subjected to sub-chronic restraint stress for 5 consecutive days. NIR PBM (810 nm laser, 33.3 J/cm2) and/or CoQ10 (500 mg/kg/day, gavage) were administered for five days concomitantly with immobilization. Behavior was evaluated by the forced swim test (FST), tail suspension test (TST), and open field test (OFT). Mitochondrial membrane potential as well as oxidative stress, neuroinflammatory, and markers of apoptosis were evaluated in the prefrontal cortex (PFC) and hippocampus (HIP). The serum levels of pro-inflammatory cytokines, cortisol, and corticosterone were also measured. PBM or CoQ10, or the combination, ameliorated depressive-like behaviors induced by restraint stress as indicated by decreased immobility time in both the FST and TST. PBM and/or CoQ10 treatments decreased lipid peroxidation and enhanced total antioxidant capacity (TAC), GSH levels, GPx and SOD activities in both brain areas. The neuroinflammatory response in the HIP and PFC was suppressed, as indicated by decreased NF-kB, p38, and JNK levels in PBM and/or CoQ10 groups. Intrinsic apoptosis biomarkers, BAX, Bcl-2, cytochrome c release, and caspase-3 and -9, were also significantly down-regulated by both treatments. Furthermore, both treatments decreased the elevated serum levels of cortisol, corticosterone, TNF-α, and IL-6 induced by restraint stress. Transcranial NIR PBM and CoQ10 therapies may be effective antidepressant strategies for the prevention of psychopathological and behavioral symptoms induced by stress.
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Cassano P, Petrie SR, Mischoulon D, Cusin C, Katnani H, Yeung A, De Taboada L, Archibald A, Bui E, Baer L, Chang T, Chen J, Pedrelli P, Fisher L, Farabaugh A, Hamblin MR, Alpert JE, Fava M, Iosifescu DV. Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial. Photomed Laser Surg 2018; 36:634-646. [PMID: 30346890 DOI: 10.1089/pho.2018.4490] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Objective: Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress. Materials and methods: We conducted a double-blind, sham-controlled study on the safety and efficacy [change in Hamilton Depression Rating Scale (HAM-D17) total score at end-point] of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. Results: The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. Conclusions: t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.
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Affiliation(s)
- Paolo Cassano
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.,Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston, Massachusetts
| | - Samuel R Petrie
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - David Mischoulon
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Cristina Cusin
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Husam Katnani
- Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Albert Yeung
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Abigal Archibald
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Eric Bui
- Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston, Massachusetts
| | - Lee Baer
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Trina Chang
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Justin Chen
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Paola Pedrelli
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Lauren Fisher
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Amy Farabaugh
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Michael R Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts.,Department of Dermatology, Harvard Medical School, Boston, Massachusetts.,Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts
| | - Jonathan E Alpert
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Maurizio Fava
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
| | - Dan V Iosifescu
- Adult Psychopharmacology Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
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Sabri T, Pawelek PD, Capobianco JA. Dual Activity of Rose Bengal Functionalized to Albumin-Coated Lanthanide-Doped Upconverting Nanoparticles: Targeting and Photodynamic Therapy. ACS APPLIED MATERIALS & INTERFACES 2018; 10:26947-26953. [PMID: 30028124 DOI: 10.1021/acsami.8b08919] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
A modified version of a desolvation method was used to render lanthanide-doped upconverting nanoparticles NaGdF4:Yb3+/Er3+ (Ln-UCNPs) water-dispersible and biocompatible for photodynamic therapy. Bovine serum albumin (BSA) was used as surface coating with a direct conjugation to NaGdF4:Yb3+/Er3+ nanoparticles forming a ∼2 nm thick shell. It was estimated that approximately 112 molecules of BSA were present and cross-linked per NaGdF4:Yb3+/Er3+ nanoparticle. Analysis of the BSA structural behavior on the Ln-UCNP surfaces displayed up to 80% loss of α-helical content. Modification of the Ln-UCNPs with a BSA shell prevents luminescence quenching from solvent molecules (H2O) with high energy vibrations that can interact with the excited states of the optically active ions Er3+ and Yb3+ via dipole-dipole interactions. Additionally, the photosensitizer rose bengal (RB) was conjugated to albumin on the surface of the Ln-UCNPs. Emission spectroscopy under 980 nm excitation was carried out, and an energy transfer efficiency of 63% was obtained. In vitro cell studies performed using human lung cancer cells (A549 cell line) showed that Ln-UCNPs coated with BSA were not taken by the cells. However, when RB was conjugated to BSA on the surface of the nanoparticles, cellular uptake was observed, and cytotoxicity was induced by the production of singlet oxygen under 980 nm irradiation.
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Affiliation(s)
- Tarek Sabri
- Department of Chemistry and Biochemistry and Centre for NanoScience Research , Concordia University , 7141 Sherbrooke Street West , Montreal , Quebec H4B 1R6 , Canada
| | - Peter D Pawelek
- Department of Chemistry and Biochemistry and Centre for NanoScience Research , Concordia University , 7141 Sherbrooke Street West , Montreal , Quebec H4B 1R6 , Canada
| | - John A Capobianco
- Department of Chemistry and Biochemistry and Centre for NanoScience Research , Concordia University , 7141 Sherbrooke Street West , Montreal , Quebec H4B 1R6 , Canada
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Rosso MPDO, Buchaim DV, Kawano N, Furlanette G, Pomini KT, Buchaim RL. Photobiomodulation Therapy (PBMT) in Peripheral Nerve Regeneration: A Systematic Review. Bioengineering (Basel) 2018; 5:44. [PMID: 29890728 PMCID: PMC6027218 DOI: 10.3390/bioengineering5020044] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 06/01/2018] [Accepted: 06/07/2018] [Indexed: 12/18/2022] Open
Abstract
Photobiomodulation therapy (PBMT) has been investigated because of its intimate relationship with tissue recovery processes, such as on peripheral nerve damage. Based on the wide range of benefits that the PBMT has shown and its clinical relevance, the aim of this research was to carry out a systematic review of the last 10 years, ascertaining the influence of the PBMT in the regeneration of injured peripheral nerves. The search was performed in the PubMed/MEDLINE database with the combination of the keywords: low-level laser therapy AND nerve regeneration. Initially, 54 articles were obtained, 26 articles of which were chosen for the study according to the inclusion criteria. In the qualitative aspect, it was observed that PBMT was able to accelerate the process of nerve regeneration, presenting an increase in the number of myelinated fibers and a better lamellar organization of myelin sheath, besides improvement of electrophysiological function, immunoreactivity, high functionality rate, decrease of inflammation, pain, and the facilitation of neural regeneration, release of growth factors, increase of vascular network and collagen. It was concluded that PBMT has beneficial effects on the recovery of nerve lesions, especially when related to a faster regeneration and functional improvement, despite the variety of parameters.
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Affiliation(s)
- Marcelie Priscila de Oliveira Rosso
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisola 9-75, Vila Nova Cidade Universitária, Bauru, São Paulo CEP 17012-901, Brazil.
| | - Daniela Vieira Buchaim
- Medical School, Discipline of Human Morphophysiology, University of Marilia (UNIMAR), Av. Higino Muzi Filho, 1001 Campus Universitário, Jardim Araxa, Marília, São Paulo CEP 17525-902, Brazil.
- Medical School, Discipline of Neuroanatomy, University Center of Adamantina (UNIFAI), Rua Nove de Julho, 730, Centro, Adamantina, São Paulo CEP 17800-000, Brazil.
| | - Natália Kawano
- Medical School, Discipline of Human Morphophysiology, University of Marilia (UNIMAR), Av. Higino Muzi Filho, 1001 Campus Universitário, Jardim Araxa, Marília, São Paulo CEP 17525-902, Brazil.
| | - Gabriela Furlanette
- Medical School, Discipline of Human Morphophysiology, University of Marilia (UNIMAR), Av. Higino Muzi Filho, 1001 Campus Universitário, Jardim Araxa, Marília, São Paulo CEP 17525-902, Brazil.
| | - Karina Torres Pomini
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisola 9-75, Vila Nova Cidade Universitária, Bauru, São Paulo CEP 17012-901, Brazil.
| | - Rogério Leone Buchaim
- Department of Biological Sciences (Anatomy), Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisola 9-75, Vila Nova Cidade Universitária, Bauru, São Paulo CEP 17012-901, Brazil.
- Medical School, Discipline of Human Morphophysiology, University of Marilia (UNIMAR), Av. Higino Muzi Filho, 1001 Campus Universitário, Jardim Araxa, Marília, São Paulo CEP 17525-902, Brazil.
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Esenaliev RO, Petrov IY, Petrov Y, Guptarak J, Boone DR, Mocciaro E, Weisz H, Parsley MA, Sell SL, Hellmich H, Ford JM, Pogue C, DeWitt D, Prough DS, Micci MA. Nano-Pulsed Laser Therapy Is Neuroprotective in a Rat Model of Blast-Induced Neurotrauma. J Neurotrauma 2018; 35:1510-1522. [PMID: 29562823 PMCID: PMC5998828 DOI: 10.1089/neu.2017.5249] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
We have developed a novel, non-invasive nano-pulsed laser therapy (NPLT) system that combines the benefits of near-infrared laser light (808 nm) and ultrasound (optoacoustic) waves, which are generated with each short laser pulse within the tissue. We tested NPLT in a rat model of blast-induced neurotrauma (BINT) to determine whether transcranial application of NPLT provides neuroprotective effects. The laser pulses were applied on the intact rat head 1 h after injury using a specially developed fiber-optic system. Vestibulomotor function was assessed on post-injury days (PIDs) 1–3 on the beam balance and beam walking tasks. Cognitive function was assessed on PIDs 6–10 using a working memory Morris water maze (MWM) test. BDNF and caspase-3 messenger RNA (mRNA) expression was measured by quantitative real-time PCR (qRT-PCR) in laser-captured cortical neurons. Microglia activation and neuronal injury were assessed in brain sections by immunofluorescence using specific antibodies against CD68 and active caspase-3, respectively. In the vestibulomotor and cognitive (MWM) tests, NPLT-treated animals performed significantly better than the untreated blast group and similarly to sham animals. NPLT upregulated mRNA encoding BDNF and downregulated the pro-apoptotic protein caspase-3 in cortical neurons. Immunofluorescence demonstrated that NPLT inhibited microglia activation and reduced the number of cortical neurons expressing activated caspase-3. NPLT also increased expression of BDNF in the hippocampus and the number of proliferating progenitor cells in the dentate gyrus. Our data demonstrate a neuroprotective effect of NPLT and prompt further studies aimed to develop NPLT as a therapeutic intervention after traumatic brain injury (TBI).
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Affiliation(s)
- Rinat O Esenaliev
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas.,2 Department of Neuroscience and Cell Biology, University of Texas Medical Branch , Galveston, Texas.,3 Center for Biomedical Engineering, University of Texas Medical Branch , Galveston, Texas
| | - Irene Y Petrov
- 3 Center for Biomedical Engineering, University of Texas Medical Branch , Galveston, Texas
| | - Yuriy Petrov
- 3 Center for Biomedical Engineering, University of Texas Medical Branch , Galveston, Texas
| | - Jutatip Guptarak
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Debbie R Boone
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Emanuele Mocciaro
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Harris Weisz
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Margaret A Parsley
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Stacy L Sell
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Helen Hellmich
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Jonathan M Ford
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Connor Pogue
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Douglas DeWitt
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Donald S Prough
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
| | - Maria-Adelaide Micci
- 1 Department of Anesthesiology, University of Texas Medical Branch , Galveston, Texas
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Dos Santos JGRP, Paiva WS, Teixeira MJ. Transcranial light-emitting diode therapy for neuropsychological improvement after traumatic brain injury: a new perspective for diffuse axonal lesion management. MEDICAL DEVICES-EVIDENCE AND RESEARCH 2018; 11:139-146. [PMID: 29731669 PMCID: PMC5927185 DOI: 10.2147/mder.s155356] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
The cost of traumatic brain injury (TBI) for public health policies is undeniable today. Even patients who suffer from mild TBI may persist with cognitive symptoms weeks after the accident. Most of them show no lesion in computed tomography or conventional magnetic resonance imaging, but microstructural white matter abnormalities (diffuse axonal lesion) can be found in diffusion tensor imaging. Different brain networks work together to form an important part of the cognition process, and they can be affected by TBI. The default mode network (DMN) plays an important central role in normal brain activities, presenting greater relative deactivation during more cognitively demanding tasks. After deactivation, it allows a distinct network to activate. This network (the central executive network) acts mainly during tasks involving executive functions. The salience network is another network necessary for normal executive function, and its activation leads to deactivation of the DMN. The use of red or near-infrared (NIR) light to stimulate or regenerate tissue is known as photobiomodulation. It was discovered that NIR (wavelength 800-900 nm) and red (wavelength 600 nm) light-emitting diodes (LEDs) are able to penetrate through scalp and skull and have the potential to improve the subnormal, cellular activity of compromised brain tissue. Based on this, different experimental and clinical studies were done to test LED therapy for TBI, and promising results were found. It leads us to consider developing different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients.
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Affiliation(s)
| | - Wellingson Silva Paiva
- Department of Neurological Surgery, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Manoel Jacobsen Teixeira
- Department of Neurological Surgery, University of São Paulo School of Medicine, São Paulo, Brazil
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Polesskaya O, Baranova A, Bui S, Kondratev N, Kananykhina E, Nazarenko O, Shapiro T, Nardia FB, Kornienko V, Chandhoke V, Stadler I, Lanzafame R, Myakishev-Rempel M. Optogenetic regulation of transcription. BMC Neurosci 2018; 19:12. [PMID: 29745855 PMCID: PMC5998900 DOI: 10.1186/s12868-018-0411-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Optogenetics has become widely recognized for its success in real-time control of brain neurons by utilizing non-mammalian photosensitive proteins to open or close membrane channels. Here we review a less well known type of optogenetic constructs that employs photosensitive proteins to transduce the signal to regulate gene transcription, and its possible use in medicine. One of the problems with existing gene therapies is that they could remain active indefinitely while not allowing regulated transgene production on demand. Optogenetic regulation of transcription (ORT) could potentially be used to regulate the production of a biological drug in situ, by repeatedly applying light to the tissue, and inducing expression of therapeutic transgenes when needed. Red and near infrared wavelengths, which are capable of penetration into tissues, have potential for therapeutic applications. Existing ORT systems are reviewed herein with these considerations in mind.
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Affiliation(s)
| | - Ancha Baranova
- Research Center for Medical Genetics RAMS, Moscow, Russia.,Center for the Study of Chronic Metabolic and Rare Diseases, School of Systems Biology, George Mason University, Fairfax, VA, USA.,Atlas Biomed Group, Moscow, Russia.,Moscow Institute of Physics and Technology, Dolgoprudny, Russia
| | - Sarah Bui
- Center for the Study of Chronic Metabolic and Rare Diseases, School of Systems Biology, George Mason University, Fairfax, VA, USA
| | | | | | | | | | | | | | - Vikas Chandhoke
- Center for the Study of Chronic Metabolic and Rare Diseases, School of Systems Biology, George Mason University, Fairfax, VA, USA
| | | | | | - Max Myakishev-Rempel
- Localized Therapeutics, LLC, San Diego, CA, USA. .,Vaccine Research Institute of San Diego, San Diego, CA, USA.
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50
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Brain Photobiomodulation Therapy: a Narrative Review. Mol Neurobiol 2018; 55:6601-6636. [PMID: 29327206 DOI: 10.1007/s12035-017-0852-4] [Citation(s) in RCA: 263] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 12/19/2017] [Indexed: 12/20/2022]
Abstract
Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson's disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.
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