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O'Leary JD, Main BS, Burns MP. Non-invasive therapeutics for neurotrauma: a mechanistic overview. Front Neurol 2025; 16:1560777. [PMID: 40438568 PMCID: PMC12116354 DOI: 10.3389/fneur.2025.1560777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 04/21/2025] [Indexed: 06/01/2025] Open
Abstract
Traumatic brain injury is a leading cause of death and a major risk factor for the development of both memory and motor disorders. To date, there are no proven interventions to improve patient outcome after neurotrauma. A promising avenue of treatment has emerged in the use of non-invasive therapies for recovery after brain injury. A number of non-invasive brain stimulation techniques have been developed, such as transcranial direct current stimulation, transcranial magnetic stimulation and vagus nerve stimulation, as well as low intensity ultrasound stimulation and photobiomodulation therapy. However, standardized treatment regimens have not been developed. There is a clear need to better understand the underlying mechanisms of non-invasive therapeutics on brain injury pathology so as to more effectively guide treatment strategy. Here we review the current literature of non-invasive therapies in preclinical neurotrauma and offer insight into the potential mechanism of action and novel targets for the treatment of traumatic brain injury.
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Affiliation(s)
| | | | - Mark P. Burns
- Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Centre, Washington, DC, United States
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2
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Helali H, Samani N, Tabeie F, Eiliaei S, Kheradmand A. The effectiveness of Transcranial Photobiomodulation therapy (tPBM) on reducing anxiety, depression, and opioid craving in patients undergoing methadone maintenance treatment: a double-blind, randomized, controlled trial. BMC Psychiatry 2025; 25:94. [PMID: 39901090 PMCID: PMC11792211 DOI: 10.1186/s12888-025-06555-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 01/29/2025] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND The effects of tPBMT are from influencing compounds by triggering specific reactions, which stimulate Adenosine triphosphate biosynthesis and neurogenesis. According to these effects, tPBMT has been applied as a potential treatment for various neural-related diseases. The purpose of this study was to evaluate the impact of tPBMT on reducing anxiety, depression, and opioid craving in patients undergoing MMT. METHODS This randomized controlled clinical trial included two groups of substance-dependent patients undergoing MMT. They were randomly assigned to receive tPBMT or a sham tPBMT. The intervention group received PBM in the form of Light- Emitting Diodes (LEDs) for four minutes of light exposure at 810 nm wavelength producing 250 mW/cm2 when applied to 4 mm skin depth (totaling 60 J/cm2) in both forehead locations. The levels of anxiety, depression, and opioid craving were compared between the two groups before and after the intervention, as well as at one-month and three-month follow-up assessments. RESULTS Both groups consisted of 32 (91.4%) males and 3 (8.6%) females, with the mean age of patients in the intervention group being 37.97 ± 10.58 years, and 39.66 ± 9.94 years in the control group (P = 0.495). There were no significant differences between the two groups in terms of depression, anxiety, and opioid craving scale scores before the intervention (p>0.05). However, the tPBMT group had statistically significant reductions in their scores compared to the sham tPBMT group. (p<0.05). CONCLUSION tPBMT led to significant improvements in anxiety, depression, and opioid craving among individuals in MMT, and these improvements were sustained at one month and three months after treatment, indicating a long-lasting positive effect. TRIAL REGISTRATION Trial registration: IRCT code: IRCT20210502051162N1, Approval ID: IR.SBMU.MSP.REC.1400.111, registered on 01.06.2021.
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Affiliation(s)
- Helya Helali
- Department of Psychiatry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nastaran Samani
- Department of Psychiatry, School of Medicine, Behavioral Sciences Research Center of Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Faraj Tabeie
- Department of Medical Physics, School of medicine, School of Rehabilitation Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shiva Eiliaei
- Department of Psychiatry, School of Medicine, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Kheradmand
- Department of Psychiatry, Taleghani Hospital Clinical Research Development Unit, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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3
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Wu C, Li M, Chen Z, Feng S, Deng Q, Duan R, Liu TCY, Yang L. Remote photobiomodulation ameliorates behavioral and neuropathological outcomes in a rat model of repeated closed head injury. Transl Psychiatry 2025; 15:8. [PMID: 39799140 PMCID: PMC11724958 DOI: 10.1038/s41398-025-03228-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 12/13/2024] [Accepted: 01/07/2025] [Indexed: 01/15/2025] Open
Abstract
Repeated closed-head injuries (rCHI) from activities like contact sports, falls, military combat, and traffic accidents pose a serious risk due to their cumulative impact on the brain. Often, rCHI is not diagnosed until symptoms of irreversible brain damage appear, highlighting the need for preventive measures. This study assessed the prophylactic efficacy of remote photobiomodulation (PBM) targeted at the lungs against rCHI-induced brain injury and associated behavioral deficits. Utilizing the "Marmarou" weight-drop model, rCHI was induced in rats on days 0, 5, and 10. Remote PBM, employing an 808 nm continuous wave laser, was administered daily in 2-min sessions per lung side over 20 days. Behavioral deficits were assessed through three-chamber social interaction, forced swim, grip strength, open field, elevated plus maze, and Barnes maze tests. Immunofluorescence staining and 3D reconstruction evaluated neuronal damage, apoptosis, degeneration, and the morphology of microglia and astrocytes, as well as astrocyte and microglia-mediated excessive synapse elimination. Additionally, 16S rDNA amplicon sequencing analyzed changes in the lung microbiome following remote PBM treatment. Results demonstrated that remote PBM significantly improved depressive-like behaviors, motor dysfunction, and social interaction impairment while enhancing grip strength and reducing neuronal damage, apoptosis, and degeneration induced by rCHI. Analysis of lung microbiome changes revealed an enrichment of lipopolysaccharide (LPS) biosynthesis pathways, suggesting a potential link to neuroprotection. Furthermore, remote PBM mitigated hyperactivation of cortical microglia and astrocytes and significantly reduced excessive synaptic phagocytosis by these cells, highlighting its potential as a preventive strategy for rCHI with neuroprotective effects.
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Affiliation(s)
- Chongyun Wu
- Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China
| | - Meng Li
- Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China
| | - Zhe Chen
- Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China
| | - Shu Feng
- Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China
| | - Qianting Deng
- Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China
| | - Rui Duan
- Laboratory of Regenerative Medicine in Sports Science, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, China
| | - Timon Cheng-Yi Liu
- Laboratory of Laser Sports Medicine, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, China
| | - Luodan Yang
- Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, 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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Nairuz T, Sangwoo-Cho, Lee JH. Photobiomodulation Therapy on Brain: Pioneering an Innovative Approach to Revolutionize Cognitive Dynamics. Cells 2024; 13:966. [PMID: 38891098 PMCID: PMC11171912 DOI: 10.3390/cells13110966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 05/30/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024] Open
Abstract
Photobiomodulation (PBM) therapy on the brain employs red to near-infrared (NIR) light to treat various neurological and psychological disorders. The mechanism involves the activation of cytochrome c oxidase in the mitochondrial respiratory chain, thereby enhancing ATP synthesis. Additionally, light absorption by ion channels triggers the release of calcium ions, instigating the activation of transcription factors and subsequent gene expression. This cascade of events not only augments neuronal metabolic capacity but also orchestrates anti-oxidant, anti-inflammatory, and anti-apoptotic responses, fostering neurogenesis and synaptogenesis. It shows promise for treating conditions like dementia, stroke, brain trauma, Parkinson's disease, and depression, even enhancing cognitive functions in healthy individuals and eliciting growing interest within the medical community. However, delivering sufficient light to the brain through transcranial approaches poses a significant challenge due to its limited penetration into tissue, prompting an exploration of alternative delivery methods such as intracranial and intranasal approaches. This comprehensive review aims to explore the mechanisms through which PBM exerts its effects on the brain and provide a summary of notable preclinical investigations and clinical trials conducted on various brain disorders, highlighting PBM's potential as a therapeutic modality capable of effectively impeding disease progression within the organism-a task often elusive with conventional pharmacological interventions.
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Affiliation(s)
| | | | - Jong-Ha Lee
- Department of Biomedical Engineering, Keimyung University, Daegu 42601, Republic of Korea; (T.N.); (S.-C.)
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6
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Ma H, Du Y, Xie D, Wei ZZ, Pan Y, Zhang Y. Recent advances in light energy biotherapeutic strategies with photobiomodulation on central nervous system disorders. Brain Res 2024; 1822:148615. [PMID: 37783261 DOI: 10.1016/j.brainres.2023.148615] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 09/05/2023] [Accepted: 09/29/2023] [Indexed: 10/04/2023]
Abstract
Transcranial photobiomodulation refers to irradiation of the brain through the skull using low-intensity red or near-infrared light, which is the most commonly studied method of light energy biotherapy for central nervous system disorders. The absorption of photons by specific chromophores within the cell elevates ATP synthesis, reduces oxidative stress damage, alleviates inflammation or mediates the activation of transcription factors and signaling mediators through secondary mediators, which in turn trigger downstream signaling pathways to cause a series of photobiological effects including upregulation of neurotrophic factors. Multiple mechanisms are simultaneously involved in the pathological process of central nervous system disorders. The pleiotropic treatment of transcranial photobiomodulation towards multiple targets plays a beneficial role in improving hemodynamics, neural repair and improving behaviors in central nervous system disorders such as ischemic stroke, traumatic brain injury, neurodegenerative diseases, epilepsy and depression. This review mainly introduces the mechanism and recent preclinical and clinical advances of transcranial photobiomodulation for central nervous system disorders, which will provide a reference for clinicians to understand and engage in related studies, and calls for more and larger studies to validate and develop a wider application of transcranial photobiomodulation in central nervous system.
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Affiliation(s)
- Huixuan Ma
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yitong Du
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Dan Xie
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; The People's Hospital of Wu Hai Inner Mongolia, Inner Mongolia, China
| | - Zheng Z Wei
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuhualei Pan
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, China
| | - Yongbo Zhang
- Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
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Lin H, Li D, Zhu J, Liu S, Li J, Yu T, Tuchin VV, Semyachkina-Glushkovskaya O, Zhu D. Transcranial photobiomodulation for brain diseases: review of animal and human studies including mechanisms and emerging trends. NEUROPHOTONICS 2024; 11:010601. [PMID: 38317779 PMCID: PMC10840571 DOI: 10.1117/1.nph.11.1.010601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 12/07/2023] [Accepted: 01/05/2024] [Indexed: 02/07/2024]
Abstract
The brain diseases account for 30% of all known diseases. Pharmacological treatment is hampered by the blood-brain barrier, limiting drug delivery to the central nervous system (CNS). Transcranial photobiomodulation (tPBM) is a promising technology for treating brain diseases, due to its effectiveness, non-invasiveness, and affordability. tPBM has been widely used in pre-clinical experiments and clinical trials for treating brain diseases, such as stroke and Alzheimer's disease. This review provides a comprehensive overview of tPBM. We summarize emerging trends and new discoveries in tPBM based on over one hundred references published in the past 20 years. We discuss the advantages and disadvantages of tPBM and highlight successful experimental and clinical protocols for treating various brain diseases. A better understanding of tPBM mechanisms, the development of guidelines for clinical practice, and the study of dose-dependent and personal effects hold great promise for progress in treating brain diseases.
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Affiliation(s)
- Hao Lin
- Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics – Advanced Biomedical Imaging Facility, Wuhan, China
| | - Dongyu Li
- Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics – Advanced Biomedical Imaging Facility, Wuhan, China
- Huazhong University of Science and Technology, School of Optical Electronic Information, Wuhan, China
| | - Jingtan Zhu
- Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics – Advanced Biomedical Imaging Facility, Wuhan, China
| | - Shaojun Liu
- Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics – Advanced Biomedical Imaging Facility, Wuhan, China
| | - Jingting Li
- Huazhong University of Science and Technology, School of Engineering Sciences, Wuhan, China
| | - Tingting Yu
- Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics – Advanced Biomedical Imaging Facility, Wuhan, China
| | - Valery V. Tuchin
- Saratov State University, Science Medical Center, Saratov, Russia
- Research Center of Biotechnology of the Russian Academy of Sciences, Bach Institute of Biochemistry, Moscow, Russia
- Tomsk State University, Laboratory of Laser Molecular Imaging and Machine Learning, Tomsk, Russia
| | - Oxana Semyachkina-Glushkovskaya
- Saratov State University, Science Medical Center, Saratov, Russia
- Humboldt University, Department of Physics, Berlin, Germany
| | - Dan Zhu
- Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics – Advanced Biomedical Imaging Facility, Wuhan, China
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8
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Chamkouri H, Liu Q, Zhang Y, Chen C, Chen L. Brain photobiomodulation therapy on neurological and psychological diseases. JOURNAL OF BIOPHOTONICS 2024; 17:e202300145. [PMID: 37403428 DOI: 10.1002/jbio.202300145] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/29/2023] [Accepted: 06/29/2023] [Indexed: 07/06/2023]
Abstract
Photobiomodulation (PBM) therapy is an innovative treatment for neurological and psychological conditions. Complex IV of the mitochondrial respiratory chain can be stimulated by red light, which increases ATP synthesis. In addition, the ion channels' light absorption causes the release of Ca2+, which activates transcription factors and changes gene expression. Neuronal metabolism is improved by brain PBM therapy, which also promotes synaptogenesis and neurogenesis as well as anti-inflammatory. Its depression-treating potential is attracting attention for other conditions, including Parkinson's disease and dementia. Giving enough dosage for optimum stimulation using the transcranial PBM technique is challenging because of the rapidly increasing attenuation of light transmission in tissue. Different strategies like intranasal and intracranial light delivery systems have been proposed to overcome this restriction. The most recent preclinical and clinical data on the effectiveness of brain PBM therapy are studied in this review article.
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Affiliation(s)
- Hossein Chamkouri
- School of Materials Science and Engineering, Hefei University of Technology, Hefei, China
| | - Qi Liu
- School of Materials Science and Engineering, Hefei University of Technology, Hefei, China
| | - Yuqin Zhang
- Department of Neurology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Changchun Chen
- Department of Neurology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Lei Chen
- School of Materials Science and Engineering, Hefei University of Technology, Hefei, China
- Intelligent manufacturing institute of HFUT, Hefei, China
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Iosifescu DV, Song X, Gersten MB, Adib A, Cho Y, Collins KM, Yates KF, Hurtado-Puerto AM, McEachern KM, Osorio RS, Cassano P. Protocol Report on the Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD) Study. Healthcare (Basel) 2023; 11:2017. [PMID: 37510458 PMCID: PMC10378818 DOI: 10.3390/healthcare11142017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/04/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI). METHODS In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow. CONCLUSION This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.
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Affiliation(s)
- Dan V. Iosifescu
- Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; (K.M.C.); (K.F.Y.); (R.S.O.)
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA; (X.S.); (A.A.)
| | - Xiaotong Song
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA; (X.S.); (A.A.)
| | - Maia B. Gersten
- Department of Psychiatry, Division of Neuropsychiatry, Massachusetts General Hospital, Boston, MA 02129, USA; (M.B.G.); (Y.C.); (A.M.H.-P.); (K.M.M.); (P.C.)
| | - Arwa Adib
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA; (X.S.); (A.A.)
| | - Yoonju Cho
- Department of Psychiatry, Division of Neuropsychiatry, Massachusetts General Hospital, Boston, MA 02129, USA; (M.B.G.); (Y.C.); (A.M.H.-P.); (K.M.M.); (P.C.)
- Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA
| | - Katherine M. Collins
- Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; (K.M.C.); (K.F.Y.); (R.S.O.)
| | - Kathy F. Yates
- Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; (K.M.C.); (K.F.Y.); (R.S.O.)
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA; (X.S.); (A.A.)
| | - Aura M. Hurtado-Puerto
- Department of Psychiatry, Division of Neuropsychiatry, Massachusetts General Hospital, Boston, MA 02129, USA; (M.B.G.); (Y.C.); (A.M.H.-P.); (K.M.M.); (P.C.)
| | - Kayla M. McEachern
- Department of Psychiatry, Division of Neuropsychiatry, Massachusetts General Hospital, Boston, MA 02129, USA; (M.B.G.); (Y.C.); (A.M.H.-P.); (K.M.M.); (P.C.)
| | - Ricardo S. Osorio
- Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; (K.M.C.); (K.F.Y.); (R.S.O.)
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016, USA; (X.S.); (A.A.)
| | - Paolo Cassano
- Department of Psychiatry, Division of Neuropsychiatry, Massachusetts General Hospital, Boston, MA 02129, USA; (M.B.G.); (Y.C.); (A.M.H.-P.); (K.M.M.); (P.C.)
- Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA
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Qin YY, Pan SY, Dai JR, Wang QM, Luo X, Qin ZH, Luo L. Alleviation of ischemic brain injury by exercise preconditioning is associated with modulation of autophagy and mitochondrial dynamics in cerebral cortex of female aged mice. Exp Gerontol 2023; 178:112226. [PMID: 37257699 DOI: 10.1016/j.exger.2023.112226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/17/2023] [Accepted: 05/27/2023] [Indexed: 06/02/2023]
Abstract
Evidence from clinical studies and preclinical studies supports that exercise preconditioning can not only reduce the risk of stroke but also improve brain tissue and functional outcome after stroke. It has been demonstrated that autophagy and mitochondrial dynamics are involved in ischemic stroke. However, it is still unclear whether exercise preconditioning-induced neuroprotection against stroke is associated with modulation of autophagy and mitochondrial dynamics. Although age and sex interactively affect ischemic stroke risk, incidence, and outcome, studies based on young male animals are most often used to explore the role of exercise preconditioning in the prevention of ischemic stroke. In the current study, we examined whether exercise preconditioning could modulate autophagy and mitochondrial dynamics in a brain ischemia and reperfusion (I/R) model of female aged mice. The results showed that exercise preconditioning reduced infarct volume and improved neurological deficits. Additionally, increased levels of autophagy-related proteins LC3-II/LC3-I, LC3-II, p62, Atg7, and mitophagy-related proteins Bnip3L and Parkin, as well as increased levels of mitochondrial fusion modulator Mfn2 and mitochondrial fission modulator Drp1 in the ischemic cortex of female aged mice at 12 h after I/R were present. Our results could contribute to a better understanding of exercise preconditioning-induced neuroprotection against ischemic stroke for the elderly.
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Affiliation(s)
- Yuan-Yuan Qin
- Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215009, Jiangsu Province, China; Department of Pharmacy, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215009, China
| | - Shan-Yao Pan
- School of Physical Education and Sports Science, Soochow University; Suzhou 215021, China
| | - Jia-Ru Dai
- School of Physical Education and Sports Science, Soochow University; Suzhou 215021, China
| | - Qing-Mei Wang
- Stroke Biological Recovery Laboratory, Spaulding Rehabilitation Hospital, Teaching Affiliate of Harvard Medical School, Charlestown, MA, USA
| | - Xun Luo
- Kerry Rehabilitation Medicine Research Institute, Shenzhen, China
| | - Zheng-Hong Qin
- Department of Pharmacology and Laboratory of Aging and Nervous Diseases (SZS0703); Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science; Suzhou 215123, China
| | - Li Luo
- School of Physical Education and Sports Science, Soochow University; Suzhou 215021, 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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12
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Sorokina SS, Paskevich SI, Zaichkina SI, Malkov AE, Pikalov VA. The Combined Effect of Protective Agents and Accelerated Carbon Ions on the Behavior of Mice. BIOL BULL+ 2022. [DOI: 10.1134/s1062359022120226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
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13
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Sahbaie P, Irvine KA, Shi XY, Clark JD. Monoamine control of descending pain modulation after mild traumatic brain injury. Sci Rep 2022; 12:16359. [PMID: 36175479 PMCID: PMC9522857 DOI: 10.1038/s41598-022-20292-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 09/12/2022] [Indexed: 12/25/2022] Open
Abstract
Traumatic brain injury (TBI) is a significant public health concern, with the majority of injuries being mild. Many TBI victims experience chronic pain. Unfortunately, the mechanisms underlying pain after TBI are poorly understood. Here we examined the contribution of spinal monoamine signaling to dysfunctional descending pain modulation after TBI. For these studies we used a well-characterized concussive model of mild TBI. Measurements included mechanical allodynia, the efficacy of diffuse noxious inhibitory control (DNIC) endogenous pain control pathways and lumber norepinephrine and serotonin levels. We observed that DNIC is strongly reduced in both male and female mice after mild TBI for at least 12 weeks. In naïve mice, DNIC was mediated through α2 adrenoceptors, but sensitivity to α2 adrenoceptor agonists was reduced after TBI, and reboxetine failed to restore DNIC in these mice. The intrathecal injection of ondansetron showed that loss of DNIC was not due to excess serotonergic signaling through 5-HT3 receptors. On the other hand, the serotonin-norepinephrine reuptake inhibitor, duloxetine and the serotonin selective reuptake inhibitor escitalopram both effectively restored DNIC after TBI in both male and female mice. Therefore, enhancing serotonergic signaling as opposed to noradrenergic signaling alone may be an effective pain treatment strategy after TBI.
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Affiliation(s)
- Peyman Sahbaie
- grid.168010.e0000000419368956Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305 USA ,grid.280747.e0000 0004 0419 2556Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA 94304 USA
| | - Karen-Amanda Irvine
- grid.168010.e0000000419368956Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305 USA ,grid.280747.e0000 0004 0419 2556Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA 94304 USA
| | - Xiao-you Shi
- grid.168010.e0000000419368956Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305 USA ,grid.280747.e0000 0004 0419 2556Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA 94304 USA
| | - J. David Clark
- grid.168010.e0000000419368956Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA 94305 USA ,grid.280747.e0000 0004 0419 2556Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (E4-220), Palo Alto, CA 94304 USA
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14
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Moro C, Valverde A, Dole M, Hoh Kam J, Hamilton C, Liebert A, Bicknell B, Benabid AL, Magistretti P, Mitrofanis J. The effect of photobiomodulation on the brain during wakefulness and sleep. Front Neurosci 2022; 16:942536. [PMID: 35968381 PMCID: PMC9366035 DOI: 10.3389/fnins.2022.942536] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/08/2022] [Indexed: 11/26/2022] Open
Abstract
Over the last seventy years or so, many previous studies have shown that photobiomodulation, the use of red to near infrared light on body tissues, can improve central and peripheral neuronal function and survival in both health and in disease. These improvements are thought to arise principally from an impact of photobiomodulation on mitochondrial and non-mitochondrial mechanisms in a range of different cell types, including neurones. This impact has downstream effects on many stimulatory and protective genes. An often-neglected feature of nearly all of these improvements is that they have been induced during the state of wakefulness. Recent studies have shown that when applied during the state of sleep, photobiomodulation can also be of benefit, but in a different way, by improving the flow of cerebrospinal fluid and the clearance of toxic waste-products from the brain. In this review, we consider the potential differential effects of photobiomodulation dependent on the state of arousal. We speculate that the effects of photobiomodulation is on different cells and systems depending on whether it is applied during wakefulness or sleep, that it may follow a circadian rhythm. We speculate further that the arousal-dependent photobiomodulation effects are mediated principally through a biophoton – ultra-weak light emission – network of communication and repair across the brain.
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Affiliation(s)
- Cecile Moro
- FDD and CEA-LETI, Clinatec, Université Grenoble Alpes, Grenoble, France
| | - Audrey Valverde
- FDD and CEA-LETI, Clinatec, Université Grenoble Alpes, Grenoble, France
| | - Marjorie Dole
- FDD and CEA-LETI, Clinatec, Université Grenoble Alpes, Grenoble, France
| | - Jaimie Hoh Kam
- FDD and CEA-LETI, Clinatec, Université Grenoble Alpes, Grenoble, France
| | | | - Ann Liebert
- Governance and Research Department, Sydney Adventist Hospital, Sydney, NSW, Australia
| | - Brian Bicknell
- Faculty of Health Sciences, Australian Catholic University, Sydney, NSW, Australia
| | | | - Pierre Magistretti
- FDD and CEA-LETI, Clinatec, Université Grenoble Alpes, Grenoble, France
- Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
| | - John Mitrofanis
- FDD and CEA-LETI, Clinatec, Université Grenoble Alpes, Grenoble, France
- Institute of Ophthalmology, University College London, London, United Kingdom
- *Correspondence: John Mitrofanis,
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15
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Tolentino M, Cho CC, Lyons JA. Photobiomodulation at 830 nm Reduced Nitrite Production by Peripheral Blood Mononuclear Cells Isolated from Multiple Sclerosis Subjects. Photobiomodul Photomed Laser Surg 2022; 40:480-487. [DOI: 10.1089/photob.2021.0170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Miguel Tolentino
- Biomedical Sciences Department, University of Wisconsin Milwaukee, Milwaukee, Wisconsin, USA
| | - Chi C. Cho
- College of Health Sciences, University of Wisconsin Milwaukee, Milwaukee, Wisconsin, USA
| | - Jeri-Anne Lyons
- Biomedical Sciences Department, University of Wisconsin Milwaukee, Milwaukee, Wisconsin, USA
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16
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Tolentino M, Cho CC, Lyons JA. Photobiomodulation Modulates Interleukin-10 and Interferon Gamma Production by Mononuclear Cells from Healthy Donors and Persons with Multiple Sclerosis. Photobiomodul Photomed Laser Surg 2022; 40:234-244. [DOI: 10.1089/photob.2021.0169] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Miguel Tolentino
- Biomedical Sciences, University of Wisconsin Milwaukee, Milwaukee, Wisconsin, USA
| | - Chi C. Cho
- College of Health Sciences, University of Wisconsin Milwaukee, Milwaukee, Wisconsin, USA
| | - Jeri-Anne Lyons
- Biomedical Sciences, University of Wisconsin Milwaukee, Milwaukee, Wisconsin, USA
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17
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Davies DJ, Hadis M, Di Pietro V, Lazzarino G, Forcione M, Harris G, Stevens AR, Soon WC, Goldberg Oppenheimer P, Milward M, Belli A, Palin WM. Photobiomodulation reduces hippocampal apoptotic cell death and produces a Raman spectroscopic “signature”. PLoS One 2022; 17:e0264533. [PMID: 35239693 PMCID: PMC8893683 DOI: 10.1371/journal.pone.0264533] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 02/11/2022] [Indexed: 11/18/2022] Open
Abstract
Apoptotic cell death within the brain represents a significant contributing factor to impaired post-traumatic tissue function and poor clinical outcome after traumatic brain injury. After irradiation with light in the wavelength range of 600–1200 nm (photobiomodulation), previous investigations have reported a reduction in apoptosis in various tissues. This study investigates the effect of 660 nm photobiomodulation on organotypic slice cultured hippocampal tissue of rats, examining the effect on apoptotic cell loss. Tissue optical Raman spectroscopic changes were evaluated. A significantly higher proportion of apoptotic cells 62.8±12.2% vs 48.6±13.7% (P<0.0001) per region were observed in the control group compared with the photobiomodulation group. After photobiomodulation, Raman spectroscopic observations demonstrated 1440/1660 cm-1 spectral shift. Photobiomodulation has the potential for therapeutic utility, reducing cell loss to apoptosis in injured neurological tissue, as demonstrated in this in vitro model. A clear Raman spectroscopic signal was observed after apparent optimal irradiation, potentially integrable into therapeutic light delivery apparatus for real-time dose metering.
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Affiliation(s)
- David J. Davies
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham’ Edgbaston, Birmingham, United Kingdom
- * E-mail:
| | - Mohammed Hadis
- Photobiology Research Group, School of Dentistry, College of Medical and Dental Science, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Valentina Di Pietro
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Giuseppe Lazzarino
- Department of Chemical Sciences, Laboratory of Biochemistry, University of Catania, Catania, Italy
| | - Mario Forcione
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham’ Edgbaston, Birmingham, United Kingdom
| | - Georgia Harris
- Faculty of Chemical and Biological Engineering, University of Birmingham, Birmingham, United Kingdom
| | - Andrew R. Stevens
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham’ Edgbaston, Birmingham, United Kingdom
| | - Wai Cheong Soon
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Pola Goldberg Oppenheimer
- Faculty of Chemical and Biological Engineering, University of Birmingham, Birmingham, United Kingdom
| | - Michael Milward
- Photobiology Research Group, School of Dentistry, College of Medical and Dental Science, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Antonio Belli
- Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham’ Edgbaston, Birmingham, United Kingdom
| | - William M. Palin
- Photobiology Research Group, School of Dentistry, College of Medical and Dental Science, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom
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18
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Cardoso FDS, Mansur FCB, Lopes-Martins RÁB, Gonzalez-Lima F, Gomes da Silva S. Transcranial Laser Photobiomodulation Improves Intracellular Signaling Linked to Cell Survival, Memory and Glucose Metabolism in the Aged Brain: A Preliminary Study. Front Cell Neurosci 2021; 15:683127. [PMID: 34539346 PMCID: PMC8446546 DOI: 10.3389/fncel.2021.683127] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 08/11/2021] [Indexed: 11/16/2022] Open
Abstract
Aging is often accompanied by exacerbated activation of cell death-related signaling pathways and decreased energy metabolism. We hypothesized that transcranial near-infrared laser may increase intracellular signaling pathways beneficial to aging brains, such as those that regulate brain cell proliferation, apoptosis, and energy metabolism. To test this hypothesis, we investigated the expression and activation of intracellular signaling proteins in the cerebral cortex and hippocampus of aged rats (20 months old) treated with the transcranial near-infrared laser for 58 consecutive days. As compared to sham controls, transcranial laser treatment increased intracellular signaling proteins related to cell proliferation and cell survival, such as signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB), also known as Akt that is linked to glucose metabolism. In addition, ERK is linked to memory, while ERK and JNK signaling pathways regulate glucose metabolism. Specifically, the laser treatment caused the activation of STAT3, ERK, and JNK signaling proteins in the cerebral cortex. In the hippocampus, the laser treatment increased the expression of p70S6K and STAT3 and the activation of Akt. Taken together, the data support the hypothesis that transcranial laser photobiomodulation improves intracellular signaling pathways linked to cell survival, memory, and glucose metabolism in the brain of aged rats.
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Affiliation(s)
- Fabrízio Dos Santos Cardoso
- Núcleo de Pesquisas Tecnológicas, Universidade de Mogi das Cruzes, Mogi das Cruzes, Brazil.,Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX, United States
| | | | | | - Francisco Gonzalez-Lima
- Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, TX, United States
| | - Sérgio Gomes da Silva
- Núcleo de Pesquisas Tecnológicas, Universidade de Mogi das Cruzes, Mogi das Cruzes, Brazil.,Centro Universitário UNIFAMINAS (UNIFAMINAS), Muriaé, Brazil.,Hospital do Câncer de Muriaé, Fundação Cristiano Varella (FCV), Muriaé, Brazil
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19
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Montazeri K, Farhadi M, Fekrazad R, Akbarnejad Z, Chaibakhsh S, Mahmoudian S. Transcranial photobiomodulation in the management of brain disorders. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2021; 221:112207. [PMID: 34119804 DOI: 10.1016/j.jphotobiol.2021.112207] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/26/2021] [Accepted: 05/03/2021] [Indexed: 01/10/2023]
Abstract
Transcranial photobiomodulation (tPBM) is the process of delivering light photons through the skull to benefit from its modifying effect. Brain disorders are important health problems. The aim of this review was to determine the existing evidence of effectiveness, useful parameters, and safety of tPBM in the management of traumatic brain injury, stroke, Parkinson, and Alzheimer's disease as the common brain disorders. Four online databases, including Cochrane, Pub Med, Embase, and Google scholar were searched according to the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA) guidelines. 4728 articles were obtained in the initial search. Only those articles that were published until September 2020 and designed as randomized clinical trials (RCTs) or animal-controlled studies were included. 6 RCTs, 2 related supplementary articles, and 38 controlled animal studies met the inclusion criteria of this study. No RCTs were performed in the fields of Alzheimer's and Parkinson's diseases. The human RCTs and animal studies reported no adverse events resulted from the use of tPBM. Useful parameters of tPBM were identified according to the controlled animal studies. Since the investigated RCTs had no homogenous results, making an evidence-based decision for definite therapeutic application of tPBM is still unattainable. Altogether, these data support the need for large confirmatory well-designed RCTs for using tPBM as a novel, safe, and easy-to-administer treatment of brain disorders. EVIDENCE BEFORE THIS STUDY High prevalence and complications of brain disorders and also side effects of neuropsychiatric medications have encouraged researchers to find alternative therapeutic techniques which tPBM can be one of them. In present review we tried to determine the existing evidence of effectiveness, useful parameters, and safety of tPBM in the management of traumatic brain injury, stroke, Alzheimer, and Parkinson's disease as common brain disorders. Four online databases, including "Cochrane", "Pub Med", "Embase", and "Google scholar" were searched. Only those articles that were published until September 2020 and designed as RCTs or animal-controlled studies were included. Search keywords were the followings: transcranial photobiomodulation" OR "transcranial low-level laser therapy" AND "stroke" OR "traumatic brain injury" OR "Alzheimer" OR "Parkinson". Several studies have confirmed effectiveness of tPBM in treatment of different brain disorders but the level of evidence of its effectiveness remain to be determined. ADDED VALUE OF THIS STUDY In this study we systematically reviewed human RCTs to determine the existing evidence of tPBM effectiveness in management of four mentioned brain disorders. Since the outcomes of the reviewed RCTs were not homogeneous, further well-designed RCTs are required to decide more definitively on the evidence of this noninvasive and probably safe therapeutic intervention. We hypothesized that non-homogeneous outcomes could be due to inefficiency of PBM parameters. Controlled animal studies have the advantage of using objective tests to evaluate the results and compare them with the control group. We determined useful tPBM parameters based on these studies. IMPLICATIONS OF ALL THE AVAILABLE EVIDENCE This research is part of our main project of tinnitus treatment using photobiomodulation (PBM). Evidence of central nervous system involvement in tinnitus led us to believe that treatment protocol of tinnitus should also include transcranial PBM. The determined useful parameters can be helpful in designing more efficient tPBM protocols in the management of brain disorders and tinnitus as a common debilitating symptom that can be associated with these disorders.
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Affiliation(s)
- Katayoon Montazeri
- ENT and Head & Neck Research Center, The Five Senses Health eInstitute, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mohammad Farhadi
- ENT and Head & Neck Research Center, The Five Senses Health eInstitute, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Reza Fekrazad
- Radiation Sciences Research Center, Laser Research Center in Medical Sciences, AJA University of Medical Sciences, Tehran, Iran
| | - Zeinab Akbarnejad
- ENT and Head & Neck Research Center, The Five Senses Health eInstitute, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Samira Chaibakhsh
- Neuromusculoskeletal Research Center, Firoozgar Hospital, Iran; Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Saeid Mahmoudian
- ENT and Head & Neck Research Center, The Five Senses Health eInstitute, Iran University of Medical Sciences (IUMS), Tehran, Iran.
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20
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Zhang R, Wang J, Huang L, Wang TJ, Huang Y, Li Z, He J, Sun C, Wang J, Chen X, Wang J. The pros and cons of motor, memory, and emotion-related behavioral tests in the mouse traumatic brain injury model. Neurol Res 2021; 44:65-89. [PMID: 34308784 DOI: 10.1080/01616412.2021.1956290] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Traumatic brain injury (TBI) is a medical emergency with high morbidity and mortality. Motor, memory, and emotion-related deficits are common symptoms following TBI, yet treatment is very limited. To develop new drugs and find new therapeutic avenues, a wide variety of TBI models have been established to mimic the heterogeneity of TBI. In this regard, along with histologic measures, behavioral functional outcomes provide valuable insight into the underlying neuropathology and guide neurorehabilitation efforts for neuropsychiatric impairment after TBI. Development, characterization, and application of behavioral tests that can assess functional neurologic deficits are essential to the development of translational therapies. This comprehensive review aims to summarize 19 common behavioral tests from three aspects (motor, memory, and emotion-related) that are associated with TBI pathology. Discussion covers the apparatus, the test steps, the evaluation indexes, data collection and analysis, animal performance and applications, advantages and disadvantages as well as precautions to eliminate bias wherever possible. We discussed recent studies on TBI-related preconditioning, biomarkers, and optimized behavioral protocols. The neuropsychologic tests employed in clinics were correlated with those used in mouse TBI models. In summary, this review provides a comprehensive, up-to-date reference for TBI researchers to choose the right neurobehavioral protocol according to the research objectives of their translational investigation.
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Affiliation(s)
- Ruoyu Zhang
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Junming Wang
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Leo Huang
- Department of Psychology, University of Toronto, Toronto, Canada
| | - Tom J Wang
- Winston Churchill High School, Potomac, Maryland, USA
| | - Yinrou Huang
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Zefu Li
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jinxin He
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Chen Sun
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jing Wang
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Xuemei Chen
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jian Wang
- Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
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21
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Keshri GK, Kumar G, Sharma M, Bora K, Kumar B, Gupta A. Photobiomodulation effects of pulsed-NIR laser (810 nm) and LED (808 ± 3 nm) with identical treatment regimen on burn wound healing: A quantitative label-free global proteomic approach. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY 2021. [DOI: 10.1016/j.jpap.2021.100024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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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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Correia Rocha IR, Chacur M. Modulatory effects of photobiomodulation in the anterior cingulate cortex of diabetic rats. Photochem Photobiol Sci 2021; 20:781-790. [PMID: 34053000 DOI: 10.1007/s43630-021-00059-1] [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: 03/12/2021] [Accepted: 05/25/2021] [Indexed: 10/21/2022]
Abstract
Anterior Cingulate Cortex (ACC) has a crucial contribution to higher order pain processing. Photobiomodulation (PBM) has being used as integrative medicine for pain treatment and for a variety of nervous system disorders. This study evaluated the effects of PBM in the ACC of diabetic rats. Type 1 diabetes was induced by a single dose of streptozotocin (85 mg/Kg). A total of ten sessions of PBM (pulsed gallium-arsenide laser, 904 nm, 9500 Hz, 6.23 J/cm2) was applied to the rat peripheral nervous system. Glial fibrillary acidic protein (GFAP), mu-opioid receptor (MOR), glutamate receptor 1 (GluR1), and glutamic acid decarboxylase (GAD65/67) protein level expression were analyzed in the ACC of diabetic rats treated with PBM. Our data revealed that PBM decreased 79.5% of GFAP protein levels in the ACC of STZ rats. Moreover, STZ + PBM rats had protein levels of MOR increased 14.7% in the ACC. Interestingly, STZ + PBM rats had a decrease in 70.7% of GluR1 protein level in the ACC. Additionally, PBM decreased 45.5% of GAD65/67 protein levels in the ACC of STZ rats.
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Affiliation(s)
- Igor Rafael Correia Rocha
- Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenue Lineu Prestes 2415, room 007, São Paulo, 05508-900, Brazil
| | - Marucia Chacur
- Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenue Lineu Prestes 2415, room 007, São Paulo, 05508-900, Brazil.
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Osiac E, Mitran SI, Manea CN, Cojocaru A, Rosu G, Osiac M, Pirici DN, Bălșeanu AT, Cătălin B. Optical coherence tomography microscopy in experimental traumatic brain injury. Microsc Res Tech 2021; 84:422-431. [PMID: 33009699 PMCID: PMC7891427 DOI: 10.1002/jemt.23599] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 08/19/2020] [Accepted: 08/30/2020] [Indexed: 12/28/2022]
Abstract
Worldwide elderly traumatic brain injury (TBI) patients tend to become an increasing burden to the society. Thus, a faster and less expensive way of evaluating TBI victims is needed. In the present study we investigated if optical coherence tomography (OCT) could be used as such a method. By using an animal model, we established if OCT can detect cortical changes in the acute phase of a penetrating TBI, in young (5-7 months) and old (20-22 months) rats. Due to the long-term evolution of TBI's, we wanted to investigate to what extent OCT could detect changes within the cortex in the chronic phase. Adult (7-12 months) male rats were used. Surprisingly, OCT imaging of the normal hemisphere was able to discriminate age-related differences in the mean gray values (MGV) of recorded pixels (p = .032). Furthermore, in the acute phase of TBI, OCT images recorded at 24 hr after the injury showed differences between the apparent damaged area of young and aged animals. Changes of MGV and skewness were only recorded 48 hr after injury. Monitoring the chronical evolution of the TBI with OCT revealed changes over time exceeding the normal range recorded for MGV, skewness and kurtosis, 14 and 21 days after TBI. Although in the present study we still used an extremely invasive approach, as technology improves, less invasive and non-harmful ways of recording OCT may allow for an objective way to detect changes within the brain structure after brain injuries.
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Affiliation(s)
- Eugen Osiac
- Experimental Research Center for Normal and Pathological AgingUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
- Department of BiophysicsUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
| | - Smaranda Ioana Mitran
- Experimental Research Center for Normal and Pathological AgingUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
- Department of PhysiologyUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
| | - Cătălin Nicolae Manea
- Experimental Research Center for Normal and Pathological AgingUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
- Department of Informatics, Communication and StatisticsUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
| | - Alexandru Cojocaru
- Department of PhysiologyUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
| | - Gabriela‐Camelia Rosu
- Department of Research MethodologyUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
| | - Mariana Osiac
- Department of Physics, Faculty of ScienceUniversity of CraiovaCraiovaRomania
| | - Daniel Nicolae Pirici
- Department of Research MethodologyUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
| | - Adrian Tudor Bălșeanu
- Experimental Research Center for Normal and Pathological AgingUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
- Department of PhysiologyUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
| | - Bogdan Cătălin
- Experimental Research Center for Normal and Pathological AgingUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
- Department of PhysiologyUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
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Martin PI, Chao L, Krengel MH, Ho MD, Yee M, Lew R, Knight J, Hamblin MR, Naeser MA. Transcranial Photobiomodulation to Improve Cognition in Gulf War Illness. Front Neurol 2021; 11:574386. [PMID: 33551948 PMCID: PMC7859640 DOI: 10.3389/fneur.2020.574386] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 11/09/2020] [Indexed: 11/21/2022] Open
Abstract
Introduction: Approximately 25-30% of veterans deployed to Kuwait, 1990-91, report persistent multi-symptom Gulf War Illness (GWI) likely from neurotoxicant exposures. Photobiomodulation (PBM) in red/near-infrared (NIR) wavelengths is a safe, non-invasive modality shown to help repair hypoxic/stressed cells. Red/NIR wavelengths are absorbed by cytochrome C oxidase in mitochondria, releasing nitric oxide (increasing local vasodilation), and increasing adenosine tri-phosphate production. We investigated whether PBM applied transcranially could improve cognition, and health symptoms in GWI. Materials and Methods: Forty-eight (40 M) participants completed this blinded, randomized, sham-controlled trial using Sham or Real, red/NIR light-emitting diodes (LED) applied transcranially. Fifteen, half-hour transcranial LED (tLED) treatments were twice a week (7.5 weeks, in-office). Goggles worn by participant and assistant maintained blinding for visible red. Pre-/Post- testing was at Entry, 1 week and 1 month post- 15th treatment. Primary outcome measures were neuropsychological (NP) tests; secondary outcomes, Psychosocial Questionnaires, including PTSD. Results: Primary Analyses (all participants), showed improvement for Real vs. Sham, for Digit Span Forwards (p < 0.01); and a trend for Trails 4, Number/Letter Sequencing (p < 0.10). For secondary outcomes, Real group reported more improvement on the SF-36V Plus, Physical Component Score (p < 0.08). Secondary Analyses included only subjects scoring below norm (50%ile) at Entry, on specific NP test/s. Real and Sham improved at 1 week after 15th treatment; however, at 1 month, only those receiving Real improved further: Digit Span Total, Forwards and Backwards; Trails 4, Number/Letter Sequencing; California Verbal Learning Test-II, long delay free recall; Continuous Performance Test-II, False Alarm Rate; and Color-Word Interference, Stroop, Trial 3, Inhibition; Sham group worsened, toward Entry values. Only those with more post-traumatic stress disorder (PTSD) symptomatology at Entry, receiving Real, continued to have additional PTSD reduction at 1 month; Sham regressed. Conclusion: This study was underpowered (n = 48), with large heterogeneity at Entry. This likely contributed to significance or trend to significance, for only two of the NP tests (Digit Span Forwards; Trails 4, Number/Letter Sequencing) and only one general health measure, the SF-36V Plus, Physical Component Score. More subjects receiving Real, self-reported increased concentration, relaxation and sleep. Controlled studies with newer, transcranial LED home treatment devices are warranted; this is expected to increase enrollment. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01782378.
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Affiliation(s)
- Paula I. Martin
- VA Boston Healthcare System, Boston, MA, United States
- Department of Neurology, School of Medicine, Boston University, Boston, MA, United States
| | - Linda Chao
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States
| | - Maxine H. Krengel
- VA Boston Healthcare System, Boston, MA, United States
- Department of Neurology, School of Medicine, Boston University, Boston, MA, United States
| | - Michael D. Ho
- VA Boston Healthcare System, Boston, MA, United States
| | - Megan Yee
- VA Boston Healthcare System, Boston, MA, United States
| | - Robert Lew
- VA Boston Healthcare System, Boston, MA, United States
- Department of Biostatistics, School of Public Health, Boston University, Boston, MA, United States
| | - Jeffrey Knight
- VA Boston Healthcare System, National Center for Posttraumatic Stress Disorder, Boston, MA, United States
| | - Michael R. Hamblin
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, United States
- Laser Research Center, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
| | - Margaret A. Naeser
- VA Boston Healthcare System, Boston, MA, United States
- Department of Neurology, School of Medicine, Boston University, Boston, MA, United States
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You J, Bragin A, Liu H, Li L. Preclinical studies of transcranial photobiomodulation in the neurological diseases. TRANSLATIONAL BIOPHOTONICS 2021. [DOI: 10.1002/tbio.202000024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Affiliation(s)
- Jing You
- Department of Biomedical Engineering University of North Texas Denton Texas USA
| | - Anatol Bragin
- Department of Neurology University of California Los Angeles Los Angeles California USA
- Brain Research Institute University of California Los Angeles Los Angeles California USA
| | - Hanli Liu
- Department of Bioengineering University of Texas at Arlington Arlington Texas USA
| | - Lin Li
- Department of Biomedical Engineering University of North Texas Denton Texas USA
- Department of Neurology University of California Los Angeles Los Angeles California USA
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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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Hamdy O, Mohammed HS. Investigating the transmission profiles of 808 nm laser through different regions of the rat's head. Lasers Med Sci 2020; 36:803-810. [PMID: 32638241 DOI: 10.1007/s10103-020-03098-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 07/01/2020] [Indexed: 11/30/2022]
Abstract
Studying light penetration in biological tissues became a very important concern in various medical applications. It is an essential factor required to resolve the optical dose in many diagnostic and therapeutic procedures. The absorption and scattering properties of the inspected tissue control how deep the light will travel inside the tissue. However, these optical properties are highly dependent on the wavelength of the light source. In this work, the light transmission through different regions of the rat's head was investigated and the minimum laser power required to reach different parts of the head is also determined using 808-nm semiconductor laser diode. The power variation in different regions of the head is estimated using Monte Carlo simulation. Absorption and scattering coefficients of the head layers were calculated using integrating sphere measurements and Kubelka-Munk model. The absorption coefficient of the skin was 0.19 ± 0.071 mm-1, 0.024 ± 0.11 mm-1 for skull, and 0.35 ± 0.13 mm-1 for the brain, while the scattering coefficients were 7.35 ± 1.09, 2.71 ± 0.37, and 13.04 ± 0.36 mm-1 for skin, skull, and brain, respectively. The obtained results provide a relationship between laser incident power and the depth in the rat's head showing a higher optical transmission at the frontal part of the head than the middle or back regions due to the variations in the skull thickness. Therefore, the study revealed that the transmitted power of 808 nm laser at different incident locations on the head is nonlinear and variable due to different skull's thickness.
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Affiliation(s)
- Omnia Hamdy
- Department Of Engineering Applications of Laser, The National Institute of Laser Enhanced Sciences, Cairo University, Giza, 12613, Egypt.
| | - Haitham S Mohammed
- Biophysics Department, Faculty of Science, Cairo University, Giza, 12613, Egypt
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Foo ASC, Soong TW, Yeo TT, Lim KL. Mitochondrial Dysfunction and Parkinson's Disease-Near-Infrared Photobiomodulation as a Potential Therapeutic Strategy. Front Aging Neurosci 2020; 12:89. [PMID: 32308618 PMCID: PMC7145956 DOI: 10.3389/fnagi.2020.00089] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 03/17/2020] [Indexed: 12/21/2022] Open
Abstract
As the main driver of energy production in eukaryotes, mitochondria are invariably implicated in disorders of cellular bioenergetics. Given that dopaminergic neurons affected in Parkinson's disease (PD) are particularly susceptible to energy fluctuations by their high basal energy demand, it is not surprising to note that mitochondrial dysfunction has emerged as a compelling candidate underlying PD. A recent approach towards forestalling dopaminergic neurodegeneration in PD involves near-infrared (NIR) photobiomodulation (PBM), which is thought to enhance mitochondrial function of stimulated cells through augmenting the activity of cytochrome C oxidase. Notwithstanding this, our understanding of the neuroprotective mechanism of PBM remains far from complete. For example, studies focusing on the effects of PBM on gene transcription are limited, and the mechanism through which PBM exerts its effects on distant sites (i.e., its "abscopal effect") remains unclear. Also, the clinical application of NIR in PD proves to be challenging. Efficacious delivery of NIR light to the substantia nigra pars compacta (SNpc), the primary site of disease pathology in PD, is fraught with technical challenges. Concerted efforts focused on understanding the biological effects of PBM and improving the efficiency of intracranial NIR delivery are therefore essential for its successful clinical translation. Nonetheless, PBM represents a potential novel therapy for PD. In this review, we provide an update on the role of mitochondrial dysfunction in PD and how PBM may help mitigate the neurodegenerative process. We also discussed clinical translation aspects of this treatment modality using intracranially implanted NIR delivery devices.
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Affiliation(s)
- Aaron Song Chuan Foo
- Department of Physiology, National University of Singapore, Singapore, Singapore
- Division of Neurosurgery, Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore
| | - Tuck Wah Soong
- Department of Physiology, National University of Singapore, Singapore, Singapore
| | - Tseng Tsai Yeo
- Division of Neurosurgery, Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore
| | - Kah-Leong Lim
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Department of Research, National Neuroscience Institute, Singapore, Singapore
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30
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Liang Z, Lei T, Wang S, Zuo X, Li K, Song J, Sun J, Zhang J, Zheng Q, Kang X, Ma Y, Hu X, Ding T, Wang Z. Photobiomodulation by diffusing optical fiber on spinal cord: A feasibility study in piglet model. JOURNAL OF BIOPHOTONICS 2020; 13:e201960022. [PMID: 31670897 DOI: 10.1002/jbio.201960022] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 09/27/2019] [Accepted: 10/16/2019] [Indexed: 06/10/2023]
Abstract
Previous studies on spinal cord injury (SCI) have confirmed that percutaneous photobiomodulation (PBM) therapy can ameliorate immunoinflammatory responses at sites of injury, accelerate nerve regeneration, suppress glial scar formation and promote the subsequent recovery of locomotor function. The current study was performed to evaluate a large-animal model employing implanted optical fibers to accurately irradiate targeted spinal segments. The method's feasibility and irradiation parameters that do not cause phototoxic reaction were determined, and the methodology of irradiating the spinal cord with near-infrared light was investigated in detail. A diffusing optical fiber was implanted above the T9 spinal cord of Bama miniature pigs and used to transfer near-infrared light (810 nm) onto the spinal cord surface. After daily irradiation with 200, 300, 500 or 1000 mW for 14 days, both sides of the irradiated area of the spinal cord were assessed for temperature changes. The condition of the spinal cord and the position of optical fiber were investigated by magnetic resonance imaging (MRI), and different parameters indicating temperature increases or phototoxicity were measured on the normal spinal cord surface due to light irradiation (ie, heat shock responses, inflammatory reactions and neuronal apoptosis), and the animals' lower-limb neurological function and gait were assessed during the irradiation process. The implanted device was stable inside the freely moving animals, and light energy could be directly projected onto the spinal cord surface. The screening of different irradiation parameters preliminary showed that direct irradiation onto the spinal cord surface at 200 and 300 mW did not significantly increase the temperature, stress responses, inflammatory reactions and neural apoptosis, whereas irradiation at 500 mW slightly increased these parameters, and irradiation at 1000 mW induced a significant temperature increase, heat shock, inflammation and apoptosis responses. HE staining of spinal cord tissue sections did not reveal any significant structural changes of the tissues compared to the control group, and the neurological function and gait of all irradiated animals were normal. In this study, we established an in-vivo optical fiber implantation method, which might be safe and stable and could be used to directly project light energy onto the spinal cord surface. This study might provide a new perspective for clinical applications of PBM in acute SCI.
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Affiliation(s)
- Zhuowen Liang
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Tao Lei
- School of Biomedical Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Shuang Wang
- Institute of Photonics and Photon-Technology, Northwest University, Xi'an, Shaanxi, China
| | - Xiaoshuang Zuo
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Kun Li
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Jiwei Song
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Jiakai Sun
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Jiawei Zhang
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Qiao Zheng
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Xiaowei Kang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yangguang Ma
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Xueyu Hu
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Tan Ding
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Zhe Wang
- Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
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Hipskind SG, Grover FL, Fort TR, Helffenstein D, Burke TJ, Quint SA, Bussiere G, Stone M, Hurtado T. Pulsed Transcranial Red/Near-Infrared Light Therapy Using Light-Emitting Diodes Improves Cerebral Blood Flow and Cognitive Function in Veterans with Chronic Traumatic Brain Injury: A Case Series. PHOTOBIOMODULATION PHOTOMEDICINE AND LASER SURGERY 2020; 37:77-84. [PMID: 31050928 PMCID: PMC6390875 DOI: 10.1089/photob.2018.4489] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Objective: This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans. Background: Photobiomodulation therapy (PBMT) using LEDs has been shown to have positive effects on TBI in humans and animal models. Materials and methods: Twelve symptomatic military Veterans diagnosed with chronic TBI >18 months post-trauma received pulsed transcranial PBMT (tPBMT) using two neoprene therapy pads containing 220 infrared and 180 red LEDs, generating a power output of 3.3 W and an average power density of 6.4 mW/cm2 for 20 min, thrice per week over 6 weeks. Outcome measures included standardized neuropsychological test scores and qualitative and quantitative single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF). Results: Pulsed tPBMT significantly improved neuropsychological scores in 6 of 15 subscales (40.0%; p < 0.05; two tailed). SPECT analysis showed increase in rCBF in 8 of 12 (66.7%) study participants. Quantitative SPECT analysis revealed a significant increase in rCBF in this subgroup of study participants and a significant difference between pre-treatment and post-treatment gamma ray counts per cubic centimeter [t = 3.77, df = 7, p = 0.007, 95% confidence interval (95,543.21–21,931.82)]. This is the first study to report quantitative SPECT analysis of rCBF in regions of interest following pulsed tPBMT with LEDs in TBI. Conclusions: Pulsed tPBMT using LEDs shows promise in improving cognitive function and rCBF several years after TBI. Larger, controlled studies are indicated.
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Affiliation(s)
- S Gregory Hipskind
- 1 Brain Injury Consulting, LLC, Department of Brain Research, Addison, Texas.,2 InLight Medical, Medical Advisory Department, Addison, Texas
| | - Fred L Grover
- 3 Revolutionary MD, Department of Medical Research, Denver, Colorado
| | - T Richard Fort
- 4 CereScan Corporation, Department of Imaging Research, Littleton, Colorado
| | - Dennis Helffenstein
- 5 Colorado Neuropsychological Associates, Testing Department, Englewood, Colorado
| | - Thomas J Burke
- 6 University of Colorado School of Medicine, Department of Physiology (Retired), Aurora, Colorado
| | - Shane A Quint
- 4 CereScan Corporation, Department of Imaging Research, Littleton, Colorado
| | - Garrett Bussiere
- 4 CereScan Corporation, Department of Imaging Research, Littleton, Colorado
| | - Michael Stone
- 7 Veterans Administration Hospital, Department of Radiology, Las Vegas, Nevada
| | - Timothy Hurtado
- 8 Penrose-St. Francis Health Services, Emergency Department, Colorado Springs, Colorado
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Photobiomodulation therapy for management of inferior alveolar nerve injury post-extraction of impacted lower third molars. ACTA ACUST UNITED AC 2019; 4:25-32. [PMID: 33907707 DOI: 10.1007/s41547-019-00075-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Purpose Inferior alveolar nerve (IAN) injury is one of the most serious complications after extraction of impacted lower third molars. Photobiomodulation (PBM) therapy has been noted to reduce pain and inflammation while promoting tissue healing. This study examined the efficacy of PBM therapy tested in a case series of patients with postoperative IAN injury. Material and methods 20 patients with post-extraction IAN injury were involved in this study and divided into two groups. In the study group, PBM therapy (808-nm laser, 16 mW, 3 J/cm2) was used every other day for 2 weeks solely on post-extraction sockets in 10 patients diagnosed with IAN injury. In the control group, mecobalamine was prescribed to 10 patients with IAN injury. Objective and subjective recovery of IAN paresthesia was evaluated using clinical neurosensory testing and visual analog score. Results All patients showed improvement in both objective and subjective examination. Notably, the visual analog score was significantly improved after PBM treatment compared to the mecobalamine treatment (p < 0.05). Conclusion PBM therapy with 808-nm laser appears to be an effective approach to manage paresthesia post-IAN injury following impacted third molar surgery. Given the limited sample size in this study, large-scale, placebo-controlled, multi-center randomized controlled trials are needed for further validation of this innovative treatment.
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Long-term analyses of spastic muscle behavior in chronic poststroke patients after near-infrared low-level laser therapy (808 nm): a double-blinded placebo-controlled clinical trial. Lasers Med Sci 2019; 35:1459-1467. [DOI: 10.1007/s10103-019-02920-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 11/12/2019] [Indexed: 12/29/2022]
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34
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Exploring the Effects of Near Infrared Light on Resting and Evoked Brain Activity in Humans Using Magnetic Resonance Imaging. Neuroscience 2019; 422:161-171. [DOI: 10.1016/j.neuroscience.2019.10.037] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 10/20/2019] [Accepted: 10/21/2019] [Indexed: 12/12/2022]
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Fekri A, Jahan A, Moghadam Salimi M, Oskouei AE. Short-term Effects of Transcranial Near-Infrared Photobiomodulation on Motor Performance in Healthy Human Subjects: An Experimental SingleBlind Randomized Clinical Trial. J Lasers Med Sci 2019; 10:317-323. [PMID: 31875125 DOI: 10.15171/jlms.2019.51] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Introduction: Transcranial near-infrared photobiomodulation (NIR-PBM) is a new noninvasive procedure which transcranially applies a near-infrared wavelength to the scalp with a laser or a light-emitting diode (LED) source. Improvement in the neurological or psychological symptoms has been reported following light irradiation. However, to our knowledge, there is no study to investigate the effects of transcranial NIR-PBM on motor performance directly. Therefore, the objective of this study was to investigate the short-term effects of transcranial NIR-PBM on motor performance in healthy human subjects. Methods: In this experimental single-blind randomized clinical trial study, 56 right-handed healthy participants, whose ages ranged from 18 to 30, were randomly assigned to (1) Real transcranial NIR-PBMC3 group (n=14), (2) Sham transcranial NIR-PBMC3 group (n=14), (3) Real transcranial NIR-PBMC4 group (n=14), and (4) Sham transcranial NIR-PBMC4 group (n=14). We applied the 808 nm laser with irradiation energy density of 60 J/cm2 and power density of 200 mw/cm2 to the C3 or C4 points of the scalp. The number of finger taps as an indicator of motor performance was assessed by the finger-tapping test (FTT) before and after irradiation of transcranial NIR-PBM on the corresponding points of the scalp for 5 minutes. Results: The results showed that the number of finger taps in both right and left hands following the use of transcranial NIR-PBM in the real transcranial NIR-PBMC3 group significantly increased (P<0.05). Conclusion: We concluded that using transcranial NIR-PBM with a laser source on C3 point of the motor cortex in right-handed healthy people can increase the number of finger taps in both hands as an indicator of motor performance improvement.
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Affiliation(s)
- Atefeh Fekri
- Department of Physiotherapy, Faculty of Rehabilitation, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Jahan
- Department of Speech Therapy, Faculty of Rehabilitation, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Moghadam Salimi
- Department of Physiotherapy, Faculty of Rehabilitation, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali E Oskouei
- Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Wickenheisser VA, Zywot EM, Rabjohns EM, Lee HH, Lawrence DS, Tarrant TK. Laser Light Therapy in Inflammatory, Musculoskeletal, and Autoimmune Disease. Curr Allergy Asthma Rep 2019; 19:37. [PMID: 31267251 DOI: 10.1007/s11882-019-0869-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
PURPOSE OF REVIEW The goal of this review is to summarize the field to date and to discuss strengths and limitations of low-level laser (light) therapy (LLLT) for the future investigation as a treatment of inflammatory disease. RECENT FINDINGS LLLT is a promising therapeutic, particularly for those diseases of skin and joints because they are most accessible to treatment. Indeed, the known mechanisms of LLLT support its use for anti-inflammatory purposes, as well as stimulation of tissue growth and repair. Although the standard of care for the majority of inflammatory diseases is immunosuppressive agents such as corticosteroids with undesirable toxicities, LLLT offers a unique approach by being non-invasive and incurring minimal side effects. It is also relatively inexpensive and accessible and even has the possibility to be patient directed at home. There is evidence that LLLT is able to modulate the immune system at the skin and joint, and it has been shown to be efficacious in humans by affecting bacterial colonization as it may pertain to chronic rhinosinusitis. However, there is variability in the methods of laser application as well as a lack of evidence for laser type, dose-ranging studies, and wavelength selection that create barriers to the implementation of LLLT without further more rigorous and standardized study. The heterogeneity makes it difficult to draw strong conclusions about the efficacy of LLLT and its mechanisms.
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Affiliation(s)
| | - Emilia Marta Zywot
- Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, USA
| | - Emily Mary Rabjohns
- Duke Department of Medicine, Division of Rheumatology and Immunology, DUMC 3874, 200 Trent Dr., Durham, NC, 27710, USA
| | - Hyun Ho Lee
- Duke Department of Medicine, Division of Rheumatology and Immunology, DUMC 3874, 200 Trent Dr., Durham, NC, 27710, USA
| | - David S Lawrence
- Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, USA
- Department of Chemistry, University of North Carolina, Chapel Hill, USA
- Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, USA
| | - Teresa Kathleen Tarrant
- Duke School of Medicine, Durham, NC, USA.
- Duke Department of Medicine, Division of Rheumatology and Immunology, DUMC 3874, 200 Trent Dr., Durham, NC, 27710, 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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Baihui Point Laser Acupuncture Ameliorates Cognitive Impairment, Motor Deficit, and Neuronal Loss Partly via Antioxidant and Anti-Inflammatory Effects in an Animal Model of Focal Ischemic Stroke. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:1204709. [PMID: 30915140 PMCID: PMC6409074 DOI: 10.1155/2019/1204709] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 01/31/2019] [Accepted: 02/13/2019] [Indexed: 01/06/2023]
Abstract
Stroke is recognized as one of the most dangerous killer diseases in Thailand and other countries worldwide. The development of a novel strategy for treating stroke patients is therefore urgently required. The present study investigated the effect of laser acupuncture at the Baihui point on cognitive and functional recovery, neuronal loss, antioxidant enzyme activities, and interleukin-6 (IL-6) activity in the hippocampus in an animal model of focal ischemic stroke. Male Wistar rats were randomly divided into 4 groups: sham operation; permanent occlusion of the right middle cerebral artery (Rt.MCAO); Rt.MCAO with sham laser acupuncture; and Rt.MCAO with Baihui point laser acupuncture. Laser acupuncture at the Baihui point and sham acupuncture at a nonacupoint were performed once daily (10 min at each point) for 14 days after Rt.MCAO. Half of the rats in each group were examined to determine neuron density by Cresyl violet staining, while the other half were examined by biochemical assays to measure glutathione peroxidase (GSH-Px) in the hippocampus, superoxide dismutase (SOD) in mitochondria and interleukin-6 (IL-6) activity in the hippocampus. Laser acupuncture treatment was found to significantly enhance memory and neuron density in CA1 and CA3. Improved neurological score, improved GSH-Px and SOD activities, and decreased density ratio of IL-6 to β-actin were also observed in the hippocampus. In conclusion, Baihui point laser acupuncture alleviates cognitive impairment and motor deficits via antioxidant and anti-inflammatory effects in focal ischemic rats. Further study is warranted to investigate other possible mechanisms of action.
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Caldieraro MA, Cassano P. Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms. J Affect Disord 2019; 243:262-273. [PMID: 30248638 DOI: 10.1016/j.jad.2018.09.048] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 08/24/2018] [Accepted: 09/15/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Photobiomodulation (PBM) with red and near-infrared light (NIR) -also known as Low-Level Light Therapy-is a low risk, inexpensive treatment-based on non-retinal exposure-under study for several neuropsychiatric conditions. The aim of this paper is to discuss the proposed mechanism of action and to perform a systematic review of pre-clinical and clinical studies on PBM for major depressive disorder (MDD). METHODS A search on MEDLINE and EMBASE databases was performed in July 2017. No time or language restrictions were used. Studies with a primary focus on MDD and presenting original data were included (n = 17). References on the mechanisms of action of PBM also included review articles and studies not focused on MDD. RESULTS Red and NIR light penetrate the skull and modulate brain cortex; an indirect effect of red and NIR light, when delivered non-transcranially, is also postulated. The main proposed mechanism for PBM is the enhancement of mitochondrial metabolism after absorption of NIR energy by the cytochrome C oxidase; however, actions on other pathways relevant to MDD are also reported. Studies on animal models indicate a benefit from PBM that is comparable to antidepressant medications. Clinical studies also indicate a significant antidepressant effect and good tolerability. LIMITATIONS Clinical studies are heterogeneous for population and treatment parameters, and most lack an appropriate control. CONCLUSIONS Preliminary evidence supports the potential of non-retinal PBM as a novel treatment for MDD. Future studies should clarify the ideal stimulation parameters as well as the overall efficacy, effectiveness and safety profile of this treatment.
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Affiliation(s)
- Marco A Caldieraro
- Serviço de Psiquiatria, Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil.
| | - Paolo Cassano
- Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital. 1 Bowdoin Square, Boston, MA 02114, USA; Center for Anxiety and Traumatic Stress Disorders, Department of Psychiatry, Massachusetts General Hospital, Boston. 1 Bowdoin Square, MA 02114, USA
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Ganeshan V, Skladnev NV, Kim JY, Mitrofanis J, Stone J, Johnstone DM. Pre-conditioning with Remote Photobiomodulation Modulates the Brain Transcriptome and Protects Against MPTP Insult in Mice. Neuroscience 2019; 400:85-97. [PMID: 30625333 DOI: 10.1016/j.neuroscience.2018.12.050] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 12/18/2018] [Accepted: 12/30/2018] [Indexed: 12/14/2022]
Abstract
Transcranial photobiomodulation (PBM), which involves the application of low-intensity red to near-infrared light (600-1100 nm) to the head, provides neuroprotection in animal models of various neurodegenerative diseases. However, the absorption of light energy by the human scalp and skull may limit the utility of transcranial PBM in clinical contexts. We have previously shown that targeting light at peripheral tissues (i.e. "remote PBM") also provides protection of the brain in an MPTP mouse model of Parkinson's disease, suggesting remote PBM might be a viable alternative strategy for overcoming penetration issues associated with transcranial PBM. This present study aimed to determine an effective pre-conditioning regimen of remote PBM for inducing neuroprotection and elucidate the molecular mechanisms by which remote PBM enhances the resilience of brain tissue. Balb/c mice were irradiated with 670-nm light (4 J/cm2 per day) targeting dorsum and hindlimbs for 2, 5 or 10 days, followed by injection of the parkinsonian neurotoxin MPTP (50 mg/kg) over two consecutive days. Despite no direct irradiation of the head, 10 days of pre-conditioning with remote PBM significantly attenuated MPTP-induced loss of midbrain tyrosine hydroxylase-positive dopaminergic cells and mitigated the increase in FOS-positive neurons in the caudate-putamen complex. Interrogation of the midbrain transcriptome by RNA microarray and pathway enrichment analysis suggested upregulation of cell signaling and migration (including CXCR4+ stem cell and adipocytokine signaling), oxidative stress response pathways and modulation of the blood-brain barrier following remote PBM. These findings establish remote PBM preconditioning as a viable neuroprotective intervention and provide insights into the mechanisms underlying this phenomenon.
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Affiliation(s)
- Varshika Ganeshan
- Bosch Institute, University of Sydney, NSW 2006, Australia; Discipline of Physiology, University of Sydney, NSW 2006, Australia
| | - Nicholas V Skladnev
- Bosch Institute, University of Sydney, NSW 2006, Australia; Discipline of Physiology, University of Sydney, NSW 2006, Australia
| | - Ji Yeon Kim
- Bosch Institute, University of Sydney, NSW 2006, Australia; Discipline of Physiology, University of Sydney, NSW 2006, Australia; School of Medicine, University of Queensland Centre for Clinical Research, QLD 4029, Australia
| | - John Mitrofanis
- Bosch Institute, University of Sydney, NSW 2006, Australia; Discipline of Anatomy & Histology, University of Sydney, NSW 2006, Australia
| | - Jonathan Stone
- Bosch Institute, University of Sydney, NSW 2006, Australia; Discipline of Physiology, University of Sydney, NSW 2006, Australia
| | - Daniel M Johnstone
- Bosch Institute, University of Sydney, NSW 2006, Australia; Discipline of Physiology, University of Sydney, NSW 2006, Australia.
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Hipskind SG, Grover FL, Fort TR, Helffenstein D, Burke TJ, Quint SA, Bussiere G, Stone M, Hurtado T. Pulsed Transcranial Red/Near-Infrared Light Therapy Using Light-Emitting Diodes Improves Cerebral Blood Flow and Cognitive Function in Veterans with Chronic Traumatic Brain Injury: A Case Series. Photomed Laser Surg 2018:pho.2018.4489. [PMID: 30418082 DOI: 10.1089/pho.2018.4489] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans. BACKGROUND Photobiomodulation therapy (PBMT) using LEDs has been shown to have positive effects on TBI in humans and animal models. MATERIALS AND METHODS Twelve symptomatic military Veterans diagnosed with chronic TBI >18 months post-trauma received pulsed transcranial PBMT (tPBMT) using two neoprene therapy pads containing 220 infrared and 180 red LEDs, generating a power output of 3.3 W and an average power density of 6.4 mW/cm2 for 20 min, thrice per week over 6 weeks. Outcome measures included standardized neuropsychological test scores and qualitative and quantitative single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF). RESULTS Pulsed tPBMT significantly improved neuropsychological scores in 6 of 15 subscales (40.0%; p < 0.05; two tailed). SPECT analysis showed increase in rCBF in 8 of 12 (66.7%) study participants. Quantitative SPECT analysis revealed a significant increase in rCBF in this subgroup of study participants and a significant difference between pre-treatment and post-treatment gamma ray counts per cubic centimeter [t = 3.77, df = 7, p = 0.007, 95% confidence interval (95,543.21-21,931.82)]. This is the first study to report quantitative SPECT analysis of rCBF in regions of interest following pulsed tPBMT with LEDs in TBI. CONCLUSIONS Pulsed tPBMT using LEDs shows promise in improving cognitive function and rCBF several years after TBI. Larger, controlled studies are indicated.
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Affiliation(s)
- S Gregory Hipskind
- 1 Brain Injury Consulting, LLC , Department of Brain Research, Addison, Texas
- 2 InLight Medical , Medical Advisory Department, Addison, Texas
| | - Fred L Grover
- 3 Revolutionary MD , Department of Medical Research, Denver, Colorado
| | - T Richard Fort
- 4 CereScan Corporation , Department of Imaging Research, Littleton, Colorado
| | - Dennis Helffenstein
- 5 Colorado Neuropsychological Associates , Testing Department, Englewood, Colorado
| | - Thomas J Burke
- 6 University of Colorado School of Medicine, Department of Physiology (Retired) , Aurora, Colorado
| | - Shane A Quint
- 4 CereScan Corporation , Department of Imaging Research, Littleton, Colorado
| | - Garrett Bussiere
- 4 CereScan Corporation , Department of Imaging Research, Littleton, Colorado
| | - Michael Stone
- 7 Veterans Administration Hospital , Department of Radiology, Las Vegas, Nevada
| | - Timothy Hurtado
- 8 Penrose-St. Francis Health Services , Emergency Department, Colorado Springs, Colorado
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Duarte KCN, Soares TT, Magri AMP, Garcia LA, Le Sueur-Maluf L, Renno ACM, Monteiro de Castro G. Low-level laser therapy modulates demyelination in mice. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2018; 189:55-65. [PMID: 30312921 DOI: 10.1016/j.jphotobiol.2018.09.024] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 08/28/2018] [Accepted: 09/25/2018] [Indexed: 11/15/2022]
Abstract
There are no effective therapies for remyelination. Low-level laser therapy (LLLT) has been found advantageous in neurogenesis promotion, cell death prevention, and modulation of inflammation in central and peripheral nervous system models. The purpose of this study was to analyse LLLT effects on cuprizone-induced demyelination. Mice were randomly distributed into three groups: Control Laser (CTL), Cuprizone (CPZ), and Cuprizone Laser (CPZL). Mice from CPZ and CPZL groups were exposed to a 0.2% cuprizone oral diet for four complete weeks. Six sessions of transcranial laser irradiation were applied on three consecutive days, during the third and fourth weeks, with parameters of 36 J/cm2, 50 mW, 0.028 cm2 spot area, continuous wave, 1 J, 20 s, 1.78 W/cm2 in a single point equidistant between the eyes and ears of CTL and CPZL mice. Motor coordination was assessed by the rotarod test. Twenty-four hours after the last laser session, all animals were euthanized, and brains were extracted. Serum was obtained for lactate dehydrogenase toxicity testing. Histomorphological analyses consisted of Luxol Fast Blue staining and immunohistochemistry. The results showed that laser-treated animals presented motor performance improvement, attenuation of demyelination, increased number of oligodendrocyte precursor cells, modulated microglial and astrocytes activation, and a milder toxicity by cuprizone. Although further studies are required, it is suggested that LLLT represents a feasible therapy for demyelinating diseases.
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Affiliation(s)
- Katherine Chuere Nunes Duarte
- Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil
| | - Thaís Torres Soares
- Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil
| | - Angela Maria Paiva Magri
- Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil
| | - Lívia Assis Garcia
- Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil
| | - Luciana Le Sueur-Maluf
- Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil
| | - Ana Cláudia Muniz Renno
- Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil; Programa de Bioprodutos e Bioprocessos, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil
| | - Gláucia Monteiro de Castro
- Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil.
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Photobiomodulation of extracellular matrix enzymes in human nucleus pulposus cells as a potential treatment for intervertebral disk degeneration. Sci Rep 2018; 8:11654. [PMID: 30076336 PMCID: PMC6076240 DOI: 10.1038/s41598-018-30185-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 07/24/2018] [Indexed: 12/18/2022] Open
Abstract
Intervertebral disc (IVD) degeneration is associated with imbalances between catabolic and anabolic responses, regulated by extracellular matrix (ECM)-modifying enzymes such as matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs). Potential contributing factors, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, derived from infiltrated, activated macrophages within IVD tissues, can trigger abnormal production of ECM-modifying enzymes and progression of IVD degeneration. Novel therapies for regulating ECM-modifying enzymes can prevent or ameliorate IVD degeneration. Photobiomodulation (PBM), known to regulate wound repair, exhibits regenerative potential by modulating biological molecules. This study examined the effects of PBM, administered at various wavelengths (630, 525, and 465 nm) and energy densities (16, 32, and 64 J/cm2), on the production of ECM-modifying enzymes in replicated degenerative IVD. Our results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.
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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: 265] [Impact Index Per Article: 37.9] [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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Yang L, Tucker D, Dong Y, Wu C, Lu Y, Li Y, Zhang J, Liu TCY, Zhang Q. Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells. Exp Neurol 2018; 299:86-96. [PMID: 29056360 PMCID: PMC5723531 DOI: 10.1016/j.expneurol.2017.10.013] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/27/2017] [Accepted: 10/17/2017] [Indexed: 12/24/2022]
Abstract
Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808nm, 350mW/cm2, total 294J at scalp level) was applied on the infarct injury area (1.8mm anterior to the bregma and 2.5mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke.
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Affiliation(s)
- Luodan Yang
- Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science, South China Normal University, Guangzhou, China; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Donovan Tucker
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Yan Dong
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Chongyun Wu
- Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science, South China Normal University, Guangzhou, China
| | - Yujiao Lu
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Yong Li
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Juan Zhang
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Timon Cheng-Yi Liu
- Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science, South China Normal University, Guangzhou, China
| | - Quanguang Zhang
- Laboratory of Laser Sports Medicine, College of Physical Education and Sports Science, South China Normal University, Guangzhou, China; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
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Thunshelle C, Hamblin MR. Transcranial Low-Level Laser (Light) Therapy for Brain Injury. Photomed Laser Surg 2017; 34:587-598. [PMID: 28001759 DOI: 10.1089/pho.2015.4051] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Low-level laser therapy (LLLT) or photobiomodulation (PBM) is a possible treatment for brain injury, including traumatic brain injury (TBI). METHODS We review the fundamental mechanisms at the cellular and molecular level and the effects on the brain are discussed. There are several contributing processes that have been proposed to lead to the beneficial effects of PBM in treating TBI such as stimulation of neurogenesis, a decrease in inflammation, and neuroprotection. Both animal and clinical trials for ischemic stroke are outlined. A number of articles have shown how transcranial LLLT (tLLLT) is effective at increasing memory, learning, and the overall neurological performance in rodent models with TBI. RESULTS Our laboratory has conducted three different studies on the effects of tLLLT on mice with TBI. The first studied pulsed against continuous laser irradiation, finding that 10 Hz pulsed was the best. The second compared four different wavelengths, discovering only 660 and 810 nm to have any effectiveness, whereas 732 and 980 nm did not. The third looked at varying regimens of daily laser treatments (1, 3, and 14 days) and found that 14 laser applications was excessive. We also review several studies of the effects of tLLLT on neuroprogenitor cells, brain-derived neurotrophic factor and synaptogenesis, immediate early response knockout mice, and tLLLT in combination therapy with metabolic inhibitors. CONCLUSIONS Finally, some clinical studies in TBI patients are covered.
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Affiliation(s)
- Connor Thunshelle
- 1 Harvard College , Cambridge, Massachusetts.,2 Wellman Center for Photomedicine , Massachusetts General Hospital, Boston, Massachusetts
| | - Michael R Hamblin
- 2 Wellman Center for Photomedicine , Massachusetts General Hospital, Boston, Massachusetts.,3 Department of Dermatology, Harvard Medical School , Boston, Massachusetts.,4 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts
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Kim S, Han SC, Gallan AJ, Hayes JP. Neurometabolic indicators of mitochondrial dysfunction in repetitive mild traumatic brain injury. Concussion 2017; 2:CNC48. [PMID: 30202587 PMCID: PMC6128012 DOI: 10.2217/cnc-2017-0013] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 07/17/2017] [Indexed: 12/21/2022] Open
Abstract
Mild traumatic brain injury (mTBI) is a significant national health concern and there is growing evidence that repetitive mTBI (rmTBI) can cause long-term change in brain structure and function. The mitochondrion has been suggested to be involved in the mechanism of TBI. There are noninvasive methods of determining mitochondrial dysfunction through biomarkers and spectroscopy. Mitochondrial dysfunction has been implicated in a variety of neurological consequences secondary to rmTBI through activation of caspases and calpains. The purpose of this review is to examine the mechanism of mitochondrial dysfunction in rmTBI and its downstream effects on neuronal cell death, axonal injury and blood–brain barrier compromise.
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Affiliation(s)
- Susan Kim
- Boston University School of Medicine, Boston, MA 02118, USA.,Boston University School of Medicine, Boston, MA 02118, USA
| | - Steve C Han
- Boston University School of Medicine, Boston, MA 02118, USA.,Boston University School of Medicine, Boston, MA 02118, USA
| | - Alexander J Gallan
- Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637, USA.,Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637, USA
| | - Jasmeet P Hayes
- National Center for PTSD, VA Boston Healthcare System, Jamaica Plain, MA 02130, USA.,Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA.,National Center for PTSD, VA Boston Healthcare System, Jamaica Plain, MA 02130, USA.,Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA
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48
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Taib T, Leconte C, Van Steenwinckel J, Cho AH, Palmier B, Torsello E, Lai Kuen R, Onyeomah S, Ecomard K, Benedetto C, Coqueran B, Novak AC, Deou E, Plotkine M, Gressens P, Marchand-Leroux C, Besson VC. Neuroinflammation, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice. PLoS One 2017; 12:e0184811. [PMID: 28910378 PMCID: PMC5599047 DOI: 10.1371/journal.pone.0184811] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 08/31/2017] [Indexed: 01/11/2023] Open
Abstract
Traumatic brain injury (TBI) results in white matter injury (WMI) that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i) neuroinflammation, (ii) WMI and (iii) behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact. (i) For neuroinflammation, IL-1b protein as well as microglial phenotypes, by gene expression for 12 microglial activation markers on isolated CD11b+ cells from brains, were studied after TBI. IL-1b protein was increased at 6 hours and 1 day. TBI induced a mixed population of microglial phenotypes with both pro-inflammatory, anti-inflammatory and immunomodulatory markers from 6 hours to 3 days post-injury. At 7 days, microglial activation was completely resolved. (ii) Three myelin proteins were assessed after TBI on ipsi- and contralateral corpus callosum, as this structure is enriched in white matter. TBI led to an increase in 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a marker of immature and mature oligodendrocyte, at 2 days post-injury; a bilateral demyelination, evaluated by myelin basic protein, from 7 days to 3 months post-injury; and an increase in myelin oligodendrocyte glycoprotein at 6 hours and 3 days post-injury. Transmission electron microscopy study revealed various myelin sheath abnormalities within the corpus callosum at 3 months post-TBI. (iii) TBI led to sensorimotor deficits at 3 days post-TBI, and late cognitive flexibility disorder evidenced by the reversal learning task of the Barnes maze 3 months after injury. These data give an overall invaluable overview of time course of neuroinflammation that could be involved in demyelination and late cognitive disorder over a time-scale of 3 months in a model of mild TBI. This model could help to validate a pharmacological strategy to prevent post-traumatic WMI and behavioral disorders following mild TBI.
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Affiliation(s)
- Toufik Taib
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Claire Leconte
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | | | - Angelo H. Cho
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Bruno Palmier
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Egle Torsello
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Rene Lai Kuen
- Cellular and Molecular Imaging Platform, CRP2, UMS 3612 CNRS, US25 INSERM, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Somfieme Onyeomah
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Karine Ecomard
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Chiara Benedetto
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Bérard Coqueran
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Anne-Catherine Novak
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Edwige Deou
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Michel Plotkine
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Pierre Gressens
- U1141 PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Catherine Marchand-Leroux
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Valérie C. Besson
- EA4475 – Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- * E-mail:
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Jittiwat J. Laser Acupuncture at GV20 Improves Brain Damage and Oxidative Stress in Animal Model of Focal Ischemic Stroke. J Acupunct Meridian Stud 2017; 10:324-330. [PMID: 29078967 DOI: 10.1016/j.jams.2017.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 08/11/2017] [Accepted: 08/16/2017] [Indexed: 01/25/2023] Open
Abstract
The burden of stroke is high and is continually increasing due to a dramatic growth in the world's elderly population. Novel therapeutic strategies are therefore required. The present study sought to determine the effect of laser acupuncture at GV20 on brain damage, oxidative-status markers in the cerebral cortex, and superoxide dismutase in the mitochondria of an animal model of focal ischemic stroke. Wistar rats, weighing 300-350 g, were divided into the following four groups: (1) control; (2) permanent occlusion of the right middle cerebral artery (Rt.MCAO) alone; (3) Rt.MCAO plus sham laser acupuncture; and (4) Rt.MCAO plus laser-acupuncture groups. Sham laser acupuncture or laser acupuncture was performed once daily at the GV20 (Baihui) acupoint for 14 days following Rt.MCAO. Half of the rats in each group were examined by 2,3,5-triphenyltetrazolium chloride staining to determine the brain infarct volume, while the other half were examined by biochemical assays to determine the malondialdehyde level, and the glutathione peroxidase, catalase, and superoxide-dismutase activities in the brain-cortex mitochondria. The results showed that laser acupuncture at GV20 significantly decreased the brain infarct volume and malondialdehyde level, and increased the catalase, glutathione peroxidase, and superoxide-dismutase activities in cerebral ischemic rats. In conclusion, laser acupuncture at GV20 decreases the brain infarct volume in cerebral ischemic rats, at least in part due to decreased oxidative stress. Further study is warranted to investigate other possible underlying mechanisms.
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Affiliation(s)
- Jinatta Jittiwat
- Faculty of Medicine, Mahasarakham University, Mahasarakham, Thailand; Integrative Complimentary Alternative Medicine Research and Development Group, Khon Kaen University, Khon Kaen, Thailand.
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Santos T, Ferreira R, Quartin E, Boto C, Saraiva C, Bragança J, Peça J, Rodrigues C, Ferreira L, Bernardino L. Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles. Acta Biomater 2017; 59:293-302. [PMID: 28673742 DOI: 10.1016/j.actbio.2017.06.044] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 06/21/2017] [Accepted: 06/28/2017] [Indexed: 01/18/2023]
Abstract
UNLABELLED Neurogenic niches constitute a powerful endogenous source of new neurons that can be used for brain repair strategies. Neuronal differentiation of these cells can be regulated by molecules such as retinoic acid (RA) or by mild levels of reactive oxygen species (ROS) that are also known to upregulate RA receptor alpha (RARα) levels. Data showed that neural stem cells from the subventricular zone (SVZ) exposed to blue light (405nm laser) transiently induced NADPH oxidase-dependent ROS, resulting in β-catenin activation and neuronal differentiation, and increased RARα levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis both in vitro and in vivo, while offering a temporal and spatial control of RA release. In conclusion, this combinatory treatment offers great advantages to potentiate neuronal differentiation, and provides an innovative and efficient application for brain regenerative therapies. STATEMENT OF SIGNIFICANCE Controlling the differentiation of stem cells would support the development of promising brain regenerative therapies. Blue light transiently increased reactive oxygen species, resulting in neuronal differentiation and increased retinoic acid receptor (RARα) levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis, while offering a temporal and spatial control of RA release. In this sense, our approach relying on the modulation of endogenous stem cells for the generation of new neurons may support the development of novel clinical therapies.
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Affiliation(s)
- Tiago Santos
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001 Covilhã, Portugal
| | - Raquel Ferreira
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001 Covilhã, Portugal
| | - Emanuel Quartin
- Biocant - Center of Innovation in Biotechnology, 3060-197 Cantanhede, Portugal
| | - Carlos Boto
- Biocant - Center of Innovation in Biotechnology, 3060-197 Cantanhede, Portugal
| | - Cláudia Saraiva
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001 Covilhã, Portugal
| | - José Bragança
- Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME), University of Algarve, 8005-139 Faro, Portugal
| | - João Peça
- CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Institute for Interdisciplinary Research, Faculty of Medicine, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal
| | - Cecília Rodrigues
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
| | - Lino Ferreira
- Biocant - Center of Innovation in Biotechnology, 3060-197 Cantanhede, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Institute for Interdisciplinary Research, Faculty of Medicine, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal
| | - Liliana Bernardino
- Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001 Covilhã, Portugal.
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