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Chen X, Han H, Jiang T, Cai G. Effects of Tai Chi on executive function, single-leg dynamic balance, and brain functional connectivity in older adults. Sci Rep 2025; 15:11838. [PMID: 40195410 PMCID: PMC11976964 DOI: 10.1038/s41598-025-93321-w] [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: 10/23/2024] [Accepted: 03/06/2025] [Indexed: 04/09/2025] Open
Abstract
Although previous studies have confirmed the beneficial effects of Tai Chi Chuan (TCC) on improving balance ability and cognitive function in older adults, the synergistic regulatory mechanisms of TCC on bilateral lower limb muscle activation symmetry, brain functional connectivity(FC) strength, and dynamic balance ability remain unclear. This study aims to investigate the effects of a 9-week TCC training program on the executive function (EF), bilateral lower limb muscle activation symmetry, single-leg dynamic balance ability, and brain FC strength in elderly individuals. It provides valuable new insights into a field that has not been extensively explored before. After 9-week training intervention, (1) The TCC group showed significant improvements in the Y-balance Test (YBTs), with enhanced symmetry in single-leg dynamic balance between the bilateral lower limbs and a significant reduction in the laterality of lower limb muscle activation. (2) TCC training strengthened the FC of related brain regions during YBTs. When performing YBTs with the left and right legs separately, the laterality of the average brain FC strength between the two tasks was significantly reduced. (3) During EF tasks, the reaction time was significantly reduced, and the concentration of oxygenated hemoglobin in the prefrontal cortex increased. Studies have shown that TCC has significantly superior intervention effects compared to brisk walking in improving neuromuscular function in older adults. Through its multisensory integration training model, TCC simultaneously enhances neuromuscular coordination and brain network collaboration efficiency, promoting the adaptive reorganization of dynamic balance control.
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Affiliation(s)
- Xiangyuan Chen
- Department of Sports and Human Sciences, Harbin Sport University, Harbin, 150008, PR China
| | - Huifeng Han
- Department of Sports and Human Sciences, Harbin Sport University, Harbin, 150008, PR China
| | - Tao Jiang
- Department of Sports and Human Sciences, Harbin Sport University, Harbin, 150008, PR China
| | - Guoliang Cai
- Department of Sports and Human Sciences, Harbin Sport University, Harbin, 150008, PR China.
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2
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Reginensi D, Ortiz DA, Denis B, Castillo S, Burillo A, Khoury N, Xu J, Dam ML, Escobar AAH, Dave KR, Perez-Pinzon MA, Gittens RA. Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke. Sci Rep 2025; 15:11921. [PMID: 40195414 PMCID: PMC11976941 DOI: 10.1038/s41598-025-95656-w] [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: 09/21/2024] [Accepted: 03/24/2025] [Indexed: 04/09/2025] Open
Abstract
Brain decellularized extracellular matrix (ECM) can be an attractive scaffold capable of mimicking the native ecosystem of the central nervous system tissue. We studied the in vitro response of neural cultures exposed to region-specific brain decellularized ECM scaffolds from three distinct neuroanatomical sections: cortex, cerebellum and remaining areas. First, each brain region was evaluated with the isotropic fractionator method to understand the cellular composition of the different cerebral areas. Second, the cerebral regions were subjected to the decellularization process and their respective characterization using molecular, histological, and ultrastructural techniques. Third, the levels of neurotrophic factors in the decellularized brain scaffold were analyzed. Fourth, we studied the region-specific brain decellularized ECM as a mimetic platform for the maturation of PC12 cells, as a unidirectional model of differentiation. Finally, in vitro studies were carried out to evaluate the cell recovery capacity of brain decellularized ECM under stroke-mimetic conditions. Our results show that region-specific brain decellularized ECM can serve as a biomimetic scaffold capable of promoting the growth of neural lineage cells and, in addition, it possesses a combination of structural and biochemical signals (e.g., neurotrophic factors) that are capable of inducing cell phenotypic changes and promote viability and cell recovery in a stroke/ischemia model in vitro.
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Affiliation(s)
- Diego Reginensi
- Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama
- Advanced Therapies, School of Medicine, Universidad de Panamá (UP), Panama, Panama
- Tissue Engineering, Faculty of Biosciences and Public Health, Universidad Especializada de las Américas (UDELAS), Panama, Panama
- Biomedical Engineering, Faculty of Health Sciences and Engineering, Universidad Latina de Panama (ULATINA), Panama, Panama
- Sistema Nacional de Investigación (SNI-SENACYT), Panama, Panama
| | - Didio Alberto Ortiz
- Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama
| | - Bernardino Denis
- Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama
- Sistema Nacional de Investigación (SNI-SENACYT), Panama, Panama
- MD-PhD Program in Clinical and Biomedical Research, School of Medicine, UP, Panama, Panama
| | - Solangel Castillo
- Advanced Therapies, School of Medicine, Universidad de Panamá (UP), Panama, Panama
- Tissue Engineering, Faculty of Biosciences and Public Health, Universidad Especializada de las Américas (UDELAS), Panama, Panama
| | - Andrea Burillo
- Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama
| | - Nathalie Khoury
- Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, USA
- Neurology Department, The Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Jing Xu
- Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, USA
- Neurology Department, The Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Maria Lucia Dam
- Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama
| | - Anthony A Hurtado Escobar
- Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama
- Biomedical Engineering, Faculty of Health Sciences and Engineering, Universidad Latina de Panama (ULATINA), Panama, Panama
| | - Kunjan R Dave
- Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, USA
- Neurology Department, The Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Miguel A Perez-Pinzon
- Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, USA
- Neurology Department, The Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Rolando A Gittens
- Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama.
- Sistema Nacional de Investigación (SNI-SENACYT), Panama, Panama.
- MD-PhD Program in Clinical and Biomedical Research, School of Medicine, UP, Panama, Panama.
- Instituto Técnico Superior Especializado (ITSE), Ave. Domingo Diaz, Tocumen Panama, Republic of Panama.
- Centro de Investigación e Innovación Educativa, Ciencia y Tecnología (CiiECYT-AIP), Panama, Panama.
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Adibi A, Adibi I, Danaei H. Anti-Tr/DNER Antibody-Associated Ataxia in a Pediatric Hodgkin Lymphoma Survivor: Successful Treatment With Plasmapheresis and IVIG. Pediatr Blood Cancer 2025; 72:e31594. [PMID: 39910728 DOI: 10.1002/pbc.31594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 02/07/2025]
Affiliation(s)
- Armin Adibi
- Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Iman Adibi
- Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamidreza Danaei
- Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran
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Marshall A, Elshafei M, Preston FG, Burgess J, Goodson N, Fallon N, Frank B, Zhao SS, Alam U. Small Fibre Pathology in Fibromyalgia: A review. Pain Ther 2025; 14:461-478. [PMID: 39806197 PMCID: PMC11914468 DOI: 10.1007/s40122-024-00696-1] [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: 10/04/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Fibromyalgia syndrome (FMS) presents a complex and challenging disorder in both the diagnosis and treatment, with emerging evidence suggesting a role of small fibre pathology (SFP) in its pathophysiology. The significance of the role of SFP in FMS remains unclear; however, recent evidence suggests degeneration and dysfunction of the peripheral nervous system, particularly small unmyelinated fibres, which may influence pathophysiology and underlying phenotype. Both skin biopsy and corneal confocal microscopy (CCM) have consistently demonstrated that ~ 50% of people with FMS have SFP. CCM, a non-invasive measure of small nerve fibres has detected small fibre loss, correlating with neuropathic pain descriptors. Additionally, quantitative sensory testing has shown abnormalities, primarily in pain pressure/mechanical pain thresholds. This narrative review provides a comprehensive understanding of the pathophysiological dimensions of FMS with a clear focus on small nerve fibres and the peripheral nervous system, offering a roadmap for future research.
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Affiliation(s)
- Anne Marshall
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
| | - Mohamed Elshafei
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
| | - Frank G Preston
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
- Liverpool University Hospitals NHS Foundation Trust, Aintree Hospital, Liverpool, UK
| | - Jamie Burgess
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
| | - Nicola Goodson
- Liverpool University Hospitals NHS Foundation Trust, Aintree Hospital, Liverpool, UK
- Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK
| | - Nicholas Fallon
- Institute of Population Health, University of Liverpool, Liverpool, UK
| | - Bernhard Frank
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK
- The Walton Centre NHS Foundation Trust, Liverpool, UK
| | - Sizheng Steven Zhao
- Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Uazman Alam
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Clinical Sciences Centre, University Hospital Aintree, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK.
- Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, Stoke-on-Trent, UK.
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Remboutsika E. The Art of Neuroregeneration De Novo and In Situ. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025. [PMID: 40131703 DOI: 10.1007/5584_2025_856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Abstract
Neuroregeneration refers to the ability of the nervous system to repair or regenerate neural components subsequently to spinal cord and traumatic brain injuries, peripheral nerve damage, and neurodegenerative diseases. Here, we discuss lead effectors of the healing process, neural stem cells, and non-invasive physical methods, for neuroregeneration de novo and in situ.
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Affiliation(s)
- Eumorphia Remboutsika
- University Research Institute of Maternal and Child Health & Precision Medicine, School of Health Sciences, National and Kapoditrian University of Athens, Athens, Greece
- Thrivus Institute for Biomedical Science and Technology, Accra, Ghana
- AENAON EYZHN, Glyfada, Athens, Greece
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Kulhánková J, Hobbs CJ, Holubová BN, Erben J, Rysová M, Musílková J, Svobodová L, Romanyuk N, Máková V. Hybrid fibres: a new path in tissue regeneration. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2025; 36:29. [PMID: 40138044 PMCID: PMC11946956 DOI: 10.1007/s10856-025-06875-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 03/03/2025] [Indexed: 03/29/2025]
Abstract
Nowadays, various forms of organosilane materials are well established in the field of regenerative medicine, but interestingly, fibrous organosilanes have yet to be described. So far, technological obstacles prevent the preparation of such fibrous materials without any presence of spinnability-supporting organic polymers, various types of surfactants, or non-polar organic solvents, which are in many cases highly toxic and economically inconvenient. Recently, these obstacles were overcome by a complex, yet simple, technology combining different science perspectives from supramolecular chemistry through material science to tissue engineering. This paper suggests a synthesis of two biomedically promising monomeric organosilane precursors, N,N´-bis(3-(triethoxysilyl)propyl)terephthalamide (BTT) and N,N´-bis(3-(triethoxysilyl)propyl)pyridine-2,6-dicarboxamide (BTP), which are submitted to a sol-gel process combined with subsequent electrospinning technology. Such a unique procedure not only allows the preparation of toxic-free organosilane fibrous mats by suitable adjustment of sol-gel and electrospinning parameters but also simplifies material production via a one-pot synthesis approach further tuneable with appropriate organosilane precursors. The BTT and BTP fibrous materials prepared displayed not only a promising interface among the materials and 3T3 fibroblast cell lines but moreover, the interaction of nanofibrous materials with stem cells has yielded encouraging outcomes. Stem cell adhesion, proliferation, and differentiation were notably enhanced in the presence of these materials, suggesting a supportive microenvironment conducive to regenerative responses. The ability of the material to modulate the cellular behaviour of stem cells holds promising implications for the development of targeted and effective regenerative therapies.
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Affiliation(s)
- Johana Kulhánková
- Faculty of Science, Humanities and Education, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec, Czech Republic
| | - Christopher J Hobbs
- Department of Nanochemistry, Institute for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec, Czech Republic
| | - Barbora Nikendey Holubová
- Department of Nanochemistry, Institute for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec, Czech Republic
| | - Jakub Erben
- Department of Nonwovens and Nanofibrous Materials, Faculty of Textile Engineering, Technical University of Liberec, Studentská 2, 461 17, Liberec, Czech Republic
| | - Miroslava Rysová
- Department of Applied Biology, Institute for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec, Czech Republic
| | - Jana Musílková
- Institute of Physiology, Czech Academy of Science, Vídeňská 1083, 142 20, Prague, Czech Republic
| | - Lucie Svobodová
- Institute of Physiology, Czech Academy of Science, Vídeňská 1083, 142 20, Prague, Czech Republic
| | - Nataliya Romanyuk
- Department of Neuroregeneration, Institute of Experimental Medicine, Czech Academy of Science, 142 20, Prague, Czech Republic
| | - Veronika Máková
- Department of Nanochemistry, Institute for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Studentská 1402/2, 461 17, Liberec, Czech Republic.
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Liao W, Shi Y, Li Z, Yin X. Advances in 3D printing combined with tissue engineering for nerve regeneration and repair. J Nanobiotechnology 2025; 23:5. [PMID: 39754257 PMCID: PMC11697815 DOI: 10.1186/s12951-024-03052-9] [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: 09/20/2024] [Accepted: 11/29/2024] [Indexed: 01/06/2025] Open
Abstract
The repair of nerve damage has long posed a challenge owing to limited self-repair capacity and the highly differentiated nature of nerves. While new therapeutic and pharmacologic interventions have emerged in neurology, their regenerative efficacy remains limited. Tissue engineering offers a promising avenue for overcoming the limitations of conventional treatments and increasing the outcomes of regenerative repair. By implanting scaffolds into damaged nerve tissue sites, the repair and functional reconstruction of nerve injuries can be significantly facilitated. The integration of three-dimensional (3D) printing technology introduces a novel approach for accurate simulation and scalably fabricating neural tissue structures. Tissue-engineered scaffolds developed through 3D printing technology are expected to be a viable therapeutic option for nerve injuries, with broad applicability and continued development. This review systematically examines recent advances in 3D printing and tissue engineering for nerve regeneration and repair. It details the basic principles and construction strategies of neural tissue engineering and explores the crucial role of 3D printing technology. Additionally, it elucidates specific applications and technical challenges associated with this integrated approach, thereby providing valuable insights into innovative strategies and pragmatic implementation within this field.
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Affiliation(s)
- Weifang Liao
- Department of Medical Laboratory, Affiliated Hospital of Jiujiang University, Jiujiang, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, China
| | - Yuying Shi
- Department of Medical Laboratory, Affiliated Hospital of Jiujiang University, Jiujiang, China
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, China
| | - Zuguang Li
- Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoping Yin
- Department of Neurology, Affiliated Hospital of Jiujiang University, No. 57 East Xunyang Road, Jiujiang, Jiangxi, 332005, China.
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, China.
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Xu Y, Trach C, Tessier T, Sinha R, Skarsgard D. Outcomes of patients receiving urgent palliative radiotherapy for advanced lung cancer: an observational study. BMC Palliat Care 2024; 23:296. [PMID: 39709422 DOI: 10.1186/s12904-024-01628-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 12/16/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND There is considerable variability in the management of patients with advanced lung cancer referred for palliative radiotherapy owing to uncertainties in prognosis and the benefit of treatment. This study presents the outcomes of patients seen in the Fast Track Lung Clinic, an urgent access palliative radiotherapy clinic, and aims to identify factors associated with treatment response and survival. METHODS Consecutive patients with advanced lung cancer seen in the Fast Track Lung Clinic between January 2014 and July 2020 were included. Patients who underwent radiotherapy were contacted beginning 30 days after radiotherapy to evaluate treatment response. Cluster bootstraps were used to compute confidence intervals for treatment response rate. Prognostic factors for treatment response and overall survival were identified using multivariable generalized estimating equations and Cox regression models, respectively. RESULTS A total of 558 patients were included, of whom 459 (82.3%) consented to palliative radiotherapy for 1053 indications. The overall treatment response rate was 70.0% (95% CI, 65.8-74.2) for indications with follow-up (70.8%). Higher response rates were observed in patients with better ECOG performance status (OR per point, 0.71; 95% CI, 0.55-0.93; P = 0.01 ) and EGFR-mutant non-small cell lung cancer (OR vs wild-type, 2.46; 95% CI, 1.35-4.51; P = 0.003 ), whereas patients treated for neurological symptoms had lower response rates (OR, 0.27; 95% CI, 0.16-0.45; P < 0.001 ). There was no difference in response rate between patients who died within 30 days of starting radiotherapy and those who survived longer (OR, 0.83; 95% CI, 0.42-1.67; P = 0.61 ). Age; ECOG performance status; smoking history; pathology; EGFR or ALK mutation status; and the presence of liver, adrenal, or brain metastases were associated with overall survival. CONCLUSIONS Palliative radiotherapy was effective for patients with advanced lung cancer, although response rates varied by patient characteristics and treatment indication. This study identified prognostic factors for radiotherapy response and overall survival that can inform treatment decisions in this population.
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Affiliation(s)
- Yang Xu
- Division of Radiation Oncology, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, T2N 4N2, Alberta, Canada.
- Department of Oncology, University of Calgary, 2500 University Drive NW, Calgary, T2N 1N4, Alberta, Canada.
| | - Celestee Trach
- Division of Radiation Oncology, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, T2N 4N2, Alberta, Canada
| | - Tracey Tessier
- Division of Radiation Oncology, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, T2N 4N2, Alberta, Canada
| | - Rishi Sinha
- Division of Radiation Oncology, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, T2N 4N2, Alberta, Canada
- Department of Oncology, University of Calgary, 2500 University Drive NW, Calgary, T2N 1N4, Alberta, Canada
| | - David Skarsgard
- Division of Radiation Oncology, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, T2N 4N2, Alberta, Canada
- Department of Oncology, University of Calgary, 2500 University Drive NW, Calgary, T2N 1N4, Alberta, Canada
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Jahan I, Harun-Ur-Rashid M, Islam MA, Sharmin F, Al Jaouni SK, Kaki AM, Selim S. Neuronal plasticity and its role in Alzheimer's disease and Parkinson's disease. Neural Regen Res 2024; 21:01300535-990000000-00637. [PMID: 39688547 DOI: 10.4103/nrr.nrr-d-24-01019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
ABSTRACT Neuronal plasticity, the brain's ability to adapt structurally and functionally, Is essential for learning, memory, and recovery from injuries. In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, this plasticity is disrupted, leading to cognitive and motor deficits. This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease. Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function, while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control. Enhancing neuronal plasticity offers therapeutic potential for these diseases. A systematic literature review was conducted using databases such as PubMed, Scopus, and Google Scholar, focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease. Data synthesis identified key themes such as synaptic mechanisms, neurogenesis, and therapeutic strategies, linking molecular insights to clinical applications. Results highlight that targeting synaptic plasticity mechanisms, such as long-term potentiation and long-term depression, shows promise. Neurotrophic factors, advanced imaging techniques, and molecular tools (e.g., clustered regularly interspaced short palindromic repeats and optogenetics) are crucial in understanding and enhancing plasticity. Current therapies, including dopamine replacement, deep brain stimulation, and lifestyle interventions, demonstrate the potential to alleviate symptoms and improve outcomes. In conclusion, enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases. Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
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Affiliation(s)
- Israt Jahan
- Genetic Engineering and Biotechnology Research Laboratory (GEBRL), Centre for Advanced Research in Sciences (CARS), University of Dhaka, Dhaka, Bangladesh
| | - Mohammad Harun-Ur-Rashid
- Department of Chemistry, International University of Business Agriculture and Technology (IUBAT), Sector 10, Uttara Model Town, Dhaka, Bangladesh
| | - Md Aminul Islam
- Genetic Engineering and Biotechnology Research Laboratory (GEBRL), Centre for Advanced Research in Sciences (CARS), University of Dhaka, Dhaka, Bangladesh
| | - Farhana Sharmin
- Department of Anatomy, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh
| | - Soad K Al Jaouni
- Department of Hematology/Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdullah M Kaki
- Department of Anesthesia and Pain Medicine, Director of Pain Clinic, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Samy Selim
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia
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Li H, Liu R, Liu J, Qu Y. The Role and Mechanism of Metformin in the Treatment of Nervous System Diseases. Biomolecules 2024; 14:1579. [PMID: 39766286 PMCID: PMC11673726 DOI: 10.3390/biom14121579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 11/29/2024] [Accepted: 12/04/2024] [Indexed: 01/11/2025] Open
Abstract
Nervous system diseases represent a significant global burden, affecting approximately 16% of the world's population and leading to disability and mortality. These conditions, encompassing both central nervous system (CNS) and peripheral nervous system (PNS) disorders, have substantial social and economic impacts. Metformin, a guanidine derivative derived from a plant source, exhibits therapeutic properties in various health conditions such as cancer, aging, immune-related disorders, polycystic ovary syndrome, cardiovascular ailments, and more. Recent studies highlight metformin's ability to cross the blood-brain barrier, stimulate neurogenesis, and provide beneficial effects in specific neurological disorders through diverse mechanisms. This review discusses the advancements in research on metformin's role and mechanisms in treating neurological disorders within both the central and peripheral nervous systems, aiming to facilitate further investigation, utilization, and clinical application of metformin in neurology.
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Affiliation(s)
- Hui Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; (H.L.); (J.L.)
- Department of General Internal Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China;
| | - Ruhui Liu
- Department of General Internal Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China;
| | - Junyan Liu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; (H.L.); (J.L.)
| | - Yi Qu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; (H.L.); (J.L.)
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Alshehri SHS, Reddy RS, Alshahrani MS, Alnakhli HH, Gautam AP, ALMohiza MA, Alyami AM, Al Adal SY, Dixit S, Alyazedi FM. Unraveling the impact of kinesiophobia on proprioception and balance: Mediation by pain, mobility, and psychological wellbeing in post-total hip replacement recovery. PLoS One 2024; 19:e0314627. [PMID: 39636869 PMCID: PMC11620456 DOI: 10.1371/journal.pone.0314627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 11/13/2024] [Indexed: 12/07/2024] Open
Abstract
This study aimed to investigate the relationships between kinesiophobia, proprioception, and limits of stability in elderly individuals post-THR. Specifically, it sought to assess the direct and indirect effects of kinesiophobia on proprioception through mediating factors such as pain intensity, functional mobility, and psychological well-being. A cross-sectional observational study was conducted with 100 participants (50 post-THR patients and 50 asymptomatic elderly controls) at King Khalid University Hospital. Kinesiophobia was measured using the Tampa Scale for Kinesiophobia (TSK), proprioception was assessed via a digital inclinometer, and limits of stability were evaluated using computerized dynamic posturography. Post-THR patients exhibited significantly higher levels of kinesiophobia (p < 0.001) and impaired proprioception (p < 0.001) compared to controls. Mediation analyses revealed that pain intensity, functional mobility, and psychological well-being partially mediated the relationship between kinesiophobia and proprioception. The Sobel tests confirmed significant mediation effects for pain intensity (Z = 3.88, p = 0.021), functional mobility (Z = 2.96, p = 0.013), and psychological well-being (Z = 2.84, p = 0.015). Kinesiophobia significantly impairs proprioception and balance in elderly individuals post-THR, with these effects being partially mediated by pain intensity, functional mobility, and psychological well-being. These findings highlight the importance of addressing psychological factors in rehabilitation programs to enhance proprioceptive function and improve postural stability, thereby optimizing recovery outcomes in the post-THR population.
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Affiliation(s)
| | - Ravi Shankar Reddy
- Program of Physical Therapy, Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Mastour Saeed Alshahrani
- Program of Physical Therapy, Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Hani Hassan Alnakhli
- Program of Physical Therapy, Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Ajay Prashad Gautam
- Program of Physical Therapy, Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Mohammad A. ALMohiza
- Department of Health Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abdullah Mohammed Alyami
- Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia
| | - Saeed Y. Al Adal
- Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia
| | - Snehil Dixit
- Program of Physical Therapy, Department of Medical Rehabilitation Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Faisal M. Alyazedi
- Physical Therapy Department, Prince Sultan Military College of Health Sciences, Al Amal, Dhahran, Saudi Arabia
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12
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Grant MT, Nelvagal HR, Tecos M, Hamed A, Swanson K, Cooper JD, Vrecenak JD. Cellular trafficking and fate mapping of cells within the nervous system after in utero hematopoietic cell transplantation. Commun Biol 2024; 7:1624. [PMID: 39638879 PMCID: PMC11621337 DOI: 10.1038/s42003-024-06847-6] [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: 12/09/2022] [Accepted: 09/05/2024] [Indexed: 12/07/2024] Open
Abstract
In utero hematopoietic cell transplantation (IUHCT) utilizes fetal immune tolerance to achieve durable chimerism without conditioning or immunosuppression during a unique window in fetal development. Though donor cells have been observed within the nervous system following in utero injection, the timeline and distribution of cellular trafficking across the blood-brain barrier following IUHCT is not well understood. We injected 20 × 106 adult bone marrow mononuclear cells intravenously at gestational age (GA) 12-17 days and found that donor cells were maximally concentrated in the brain with treatment between GA 13-14. Donor cell engraftment persisted within the brain at every timepoint analyzed and concentrated within the hindbrain with significantly more grafted cells than in the forebrain. Additionally, transplanted cells terminally differentiated into various nervous system cellular morphologies and also populated the enteric nervous system. This study is the first to document the timeline and distribution of donor cell trafficking into the immune-protected nervous system and serves as a foundation for the application of IUHCT to treat neurogenetic diseases.
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Affiliation(s)
- Matthew T Grant
- Washington University in St. Louis School of Medicine, Department of Surgery, Division of Pediatric Surgery, St. Louis, MO, USA
| | - Hemanth Ramesh Nelvagal
- Washington University in St. Louis School of Medicine, Department of Pediatrics, Division of Genetics and Genomics, St. Louis, MO, USA
- University College London, School of Pharmacy, Department of Pharmacology, London, UK
| | - Maria Tecos
- Washington University in St. Louis School of Medicine, Department of Surgery, Division of Pediatric Surgery, St. Louis, MO, USA
| | - Amal Hamed
- Washington University in St. Louis School of Medicine, Department of Surgery, Division of Pediatric Surgery, St. Louis, MO, USA
| | - Kerry Swanson
- Washington University in St. Louis School of Medicine, Department of Surgery, Division of Pediatric Surgery, St. Louis, MO, USA
| | - Jonathan D Cooper
- Washington University in St. Louis School of Medicine, Department of Pediatrics, Division of Genetics and Genomics, St. Louis, MO, USA
| | - Jesse D Vrecenak
- Washington University in St. Louis School of Medicine, Department of Surgery, Division of Pediatric Surgery, St. Louis, MO, USA.
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13
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Lee HY, Lee JW. Spheroid-Exosome-Based Bioprinting Technology in Regenerative Medicine. J Funct Biomater 2024; 15:345. [PMID: 39590549 PMCID: PMC11595066 DOI: 10.3390/jfb15110345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/13/2024] [Accepted: 11/13/2024] [Indexed: 11/28/2024] Open
Abstract
Since the discovery that exosomes can exchange genes, their potential use as tools for tissue regeneration, disease diagnosis, and therapeutic applications has drawn significant attention. Emerging three-dimensional (3D) printing technologies, such as bioprinting, which allows the printing of cells, proteins, DNA, and other biological materials, have demonstrated the potential to create complex body tissues or personalized 3D models. The use of 3D spheroids in bioprinting facilitates volumetric tissue reconstruction and accelerates tissue regeneration via exosome secretion. In this review, we discussed a convergence approach between two promising technologies for bioprinting and exosomes in regenerative medicine. Among the various 3D cell culture methods used for exosome production, we focused on spheroids, which are suitable for mass production by bioprinting. We then summarized the research results on cases of bioprinting applications using the spheroids and exosomes produced. If a large number of spheroids can be supplied through bioprinting, the spheroid-exosome-based bioprinting technology will provide new possibilities for application in tissue regeneration, disease diagnosis, and treatment.
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Affiliation(s)
- Hwa-Yong Lee
- Division of Science Education, Kangwon National University, Chuncheon 24341, Republic of Korea;
| | - Jin Woo Lee
- Department of Molecular Medicine, College of Medicine, Gachon University, Incheon 21999, Republic of Korea
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14
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Zhang H, Jiao L, Yang S, Li H, Jiang X, Feng J, Zou S, Xu Q, Gu J, Wang X, Wei B. Brain-computer interfaces: the innovative key to unlocking neurological conditions. Int J Surg 2024; 110:5745-5762. [PMID: 39166947 PMCID: PMC11392146 DOI: 10.1097/js9.0000000000002022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 07/30/2024] [Indexed: 08/23/2024]
Abstract
Neurological disorders such as Parkinson's disease, stroke, and spinal cord injury can pose significant threats to human mortality, morbidity, and functional independence. Brain-Computer Interface (BCI) technology, which facilitates direct communication between the brain and external devices, emerges as an innovative key to unlocking neurological conditions, demonstrating significant promise in this context. This comprehensive review uniquely synthesizes the latest advancements in BCI research across multiple neurological disorders, offering an interdisciplinary perspective on both clinical applications and emerging technologies. We explore the progress in BCI research and its applications in addressing various neurological conditions, with a particular focus on recent clinical studies and prospective developments. Initially, the review provides an up-to-date overview of BCI technology, encompassing its classification, operational principles, and prevalent paradigms. It then critically examines specific BCI applications in movement disorders, disorders of consciousness, cognitive and mental disorders, as well as sensory disorders, highlighting novel approaches and their potential impact on patient care. This review reveals emerging trends in BCI applications, such as the integration of artificial intelligence and the development of closed-loop systems, which represent significant advancements over previous technologies. The review concludes by discussing the prospects and directions of BCI technology, underscoring the need for interdisciplinary collaboration and ethical considerations. It emphasizes the importance of prioritizing bidirectional and high-performance BCIs, areas that have been underexplored in previous reviews. Additionally, we identify crucial gaps in current research, particularly in long-term clinical efficacy and the need for standardized protocols. The role of neurosurgery in spearheading the clinical translation of BCI research is highlighted. Our comprehensive analysis presents BCI technology as an innovative key to unlocking neurological disorders, offering a transformative approach to diagnosing, treating, and rehabilitating neurological conditions, with substantial potential to enhance patients' quality of life and advance the field of neurotechnology.
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Affiliation(s)
- Hongyu Zhang
- Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University
- Harbin Medical University, Harbin
| | - Le Jiao
- Department of Neurosurgery, The First Hospital of Qiqihar, Qiqihar, Heilongjiang Province
| | | | | | | | - Jing Feng
- Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University
- Harbin Medical University, Harbin
| | - Shuhuai Zou
- Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University
- Harbin Medical University, Harbin
| | - Qiang Xu
- Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University
- Harbin Medical University, Harbin
| | - Jianheng Gu
- Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University
- Harbin Medical University, Harbin
| | - Xuefeng Wang
- Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University
| | - Baojian Wei
- School of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, People's Republic of China
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15
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Deokate N, Acharya S, Patil R, Shaikh SM, Karwa V. A Comprehensive Review of the Role of Stem Cells in Neuroregeneration: Potential Therapies for Neurological Disorders. Cureus 2024; 16:e67506. [PMID: 39310492 PMCID: PMC11416137 DOI: 10.7759/cureus.67506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 08/22/2024] [Indexed: 09/25/2024] Open
Abstract
Stem cell research has emerged as a groundbreaking field with significant potential for advancing neuroregeneration and neurological disorder treatment. Neurological conditions such as Alzheimer's disease, Parkinson's disease, stroke, and spinal cord injuries pose severe challenges due to their impact on quality of life and the limited efficacy of current treatments, which primarily focus on symptom management rather than addressing the underlying damage. Neuroregeneration, the process of repairing and restoring damaged neural tissues, is crucial for improving patient outcomes, given the central nervous system's limited intrinsic repair capacity. Stem cells offer a promising solution due to their ability to self-renew and differentiate into various neural cell types, providing opportunities for innovative therapies. This review provides a comprehensive analysis of the role of stem cells in neuroregeneration, exploring different types of stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells, and their mechanisms of action in neural repair. It examines current clinical trials and translational research efforts, highlighting successes and ongoing challenges such as ethical considerations, immunogenicity, and technical limitations. The review also discusses future directions in stem cell research, including advancements in gene editing, tissue engineering, and personalized medicine. By addressing these aspects, the review aims to offer a thorough understanding of the potential and challenges of stem cell-based therapies, contributing to the development of effective treatments for neurological disorders and ultimately enhancing patient quality of life.
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Affiliation(s)
- Navanath Deokate
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Sourya Acharya
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Rajvardhan Patil
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Suhail M Shaikh
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Vineet Karwa
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
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16
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Forouharshad M, Raspa A, Fortino G, Ciulla MG, Farazdaghi A, Stolojan V, Stendardo L, Bracco S, Gelain F. Biomimetic electrospun PVDF/self-assembling peptide piezoelectric scaffolds for neural stem cell transplantation in neural tissue engineering. RSC Adv 2024; 14:21277-21291. [PMID: 38974226 PMCID: PMC11225063 DOI: 10.1039/d4ra02309a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 06/29/2024] [Indexed: 07/09/2024] Open
Abstract
Piezoelectric materials can provide in situ electrical stimulation without external chemical or physical support, opening new frontiers for future bioelectric therapies. Polyvinylidene fluoride (PVDF) possesses piezoelectricity and biocompatibility, making it an electroactive biomaterial capable of enhancing bioactivity through instantaneous electrical stimulation, which indicates significant potential in tissue engineering. In this study, we developed electroactive and biomimetic scaffolds made of electrospun PVDF and self-assembling peptides (SAPs) to enhance stem cell transplantation for spinal cord injury regeneration. We investigated the morphology and crystalline polymorphs of the electrospun scaffolds. Morphological studies demonstrated the benefit of using mixed sodium dodecyl sulfate (SDS) and SAPs as additives to form thinner, uniform, and defect-free fibers. Regarding electroactive phases, β and γ phases-evidence of electroactivity-were predominant in aligned scaffolds and scaffolds modified with SDS and SAPs. In vitro studies showed that neural stem cells (NSCs) seeded on electrospun PVDF with additives exhibited desirable proliferation and differentiation compared to the gold standard. Furthermore, the orientation of the fibers influenced scaffold topography, resulting in a higher degree of cell orientation in fiber-aligned scaffolds compared to randomly oriented ones.
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Affiliation(s)
- Mahdi Forouharshad
- Center for Nanomedicine and Tissue Engineering (CNTE), ASST Grande Ospedale Metropolitano Niguarda 20162 Milan Italy
- Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies, IRCCS Casa Sollievo della Sofferenza 71013 San Giovanni Rotondo Italy
| | - Andrea Raspa
- Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies, IRCCS Casa Sollievo della Sofferenza 71013 San Giovanni Rotondo Italy
| | - Giuseppe Fortino
- Department of Biotechnology and Bioscience, University of Milano - Bicocca via R. Cozzi 55 20125 Milano Italy
| | - Maria Gessica Ciulla
- Center for Nanomedicine and Tissue Engineering (CNTE), ASST Grande Ospedale Metropolitano Niguarda 20162 Milan Italy
| | - Arman Farazdaghi
- Chemical and Biomolecular Engineering Department, Whiting School of Engineering, Johns Hopkins University MD USA
| | - Vlad Stolojan
- Advanced Technology Institute, Electrical and Electronic Engineering, University of Surrey Guildford GU2 7XH UK
| | - Luca Stendardo
- Department of Materials Science, University of Milano - Bicocca via R. Cozzi 55 20125 Milano Italy
| | - Silvia Bracco
- Department of Materials Science, University of Milano - Bicocca via R. Cozzi 55 20125 Milano Italy
| | - Fabrizio Gelain
- Center for Nanomedicine and Tissue Engineering (CNTE), ASST Grande Ospedale Metropolitano Niguarda 20162 Milan Italy
- Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies, IRCCS Casa Sollievo della Sofferenza 71013 San Giovanni Rotondo Italy
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17
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Alhadidi QM, Bahader GA, Arvola O, Kitchen P, Shah ZA, Salman MM. Astrocytes in functional recovery following central nervous system injuries. J Physiol 2024; 602:3069-3096. [PMID: 37702572 PMCID: PMC11421637 DOI: 10.1113/jp284197] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 08/07/2023] [Indexed: 09/14/2023] Open
Abstract
Astrocytes are increasingly recognised as partaking in complex homeostatic mechanisms critical for regulating neuronal plasticity following central nervous system (CNS) insults. Ischaemic stroke and traumatic brain injury are associated with high rates of disability and mortality. Depending on the context and type of injury, reactive astrocytes respond with diverse morphological, proliferative and functional changes collectively known as astrogliosis, which results in both pathogenic and protective effects. There is a large body of research on the negative consequences of astrogliosis following brain injuries. There is also growing interest in how astrogliosis might in some contexts be protective and help to limit the spread of the injury. However, little is known about how astrocytes contribute to the chronic functional recovery phase following traumatic and ischaemic brain insults. In this review, we explore the protective functions of astrocytes in various aspects of secondary brain injury such as oedema, inflammation and blood-brain barrier dysfunction. We also discuss the current knowledge on astrocyte contribution to tissue regeneration, including angiogenesis, neurogenesis, synaptogenesis, dendrogenesis and axogenesis. Finally, we discuss diverse astrocyte-related factors that, if selectively targeted, could form the basis of astrocyte-targeted therapeutic strategies to better address currently untreatable CNS disorders.
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Affiliation(s)
- Qasim M Alhadidi
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA
- Department of Pharmacy, Al-Yarmok University College, Diyala, Iraq
| | - Ghaith A Bahader
- Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA
| | - Oiva Arvola
- Division of Anaesthesiology, Jorvi Hospital, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Stem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Philip Kitchen
- College of Health and Life Sciences, Aston University, Birmingham, UK
| | - Zahoor A Shah
- Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA
| | - Mootaz M Salman
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
- Kavli Institute for NanoScience Discovery, University of Oxford, Oxford, UK
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18
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Chauhan K, Neiman AB, Tass PA. Synaptic reorganization of synchronized neuronal networks with synaptic weight and structural plasticity. PLoS Comput Biol 2024; 20:e1012261. [PMID: 38980898 PMCID: PMC11259284 DOI: 10.1371/journal.pcbi.1012261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 07/19/2024] [Accepted: 06/20/2024] [Indexed: 07/11/2024] Open
Abstract
Abnormally strong neural synchronization may impair brain function, as observed in several brain disorders. We computationally study how neuronal dynamics, synaptic weights, and network structure co-emerge, in particular, during (de)synchronization processes and how they are affected by external perturbation. To investigate the impact of different types of plasticity mechanisms, we combine a network of excitatory integrate-and-fire neurons with different synaptic weight and/or structural plasticity mechanisms: (i) only spike-timing-dependent plasticity (STDP), (ii) only homeostatic structural plasticity (hSP), i.e., without weight-dependent pruning and without STDP, (iii) a combination of STDP and hSP, i.e., without weight-dependent pruning, and (iv) a combination of STDP and structural plasticity (SP) that includes hSP and weight-dependent pruning. To accommodate the diverse time scales of neuronal firing, STDP, and SP, we introduce a simple stochastic SP model, enabling detailed numerical analyses. With tools from network theory, we reveal that structural reorganization may remarkably enhance the network's level of synchrony. When weaker contacts are preferentially eliminated by weight-dependent pruning, synchrony is achieved with significantly sparser connections than in randomly structured networks in the STDP-only model. In particular, the strengthening of contacts from neurons with higher natural firing rates to those with lower rates and the weakening of contacts in the opposite direction, followed by selective removal of weak contacts, allows for strong synchrony with fewer connections. This activity-led network reorganization results in the emergence of degree-frequency, degree-degree correlations, and a mixture of degree assortativity. We compare the stimulation-induced desynchronization of synchronized states in the STDP-only model (i) with the desynchronization of models (iii) and (iv). The latter require stimuli of significantly higher intensity to achieve long-term desynchronization. These findings may inform future pre-clinical and clinical studies with invasive or non-invasive stimulus modalities aiming at inducing long-lasting relief of symptoms, e.g., in Parkinson's disease.
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Affiliation(s)
- Kanishk Chauhan
- Department of Physics and Astronomy, Ohio University, Athens, Ohio, United States of America
- Neuroscience Program, Ohio University, Athens, Ohio, United States of America
| | - Alexander B. Neiman
- Department of Physics and Astronomy, Ohio University, Athens, Ohio, United States of America
- Neuroscience Program, Ohio University, Athens, Ohio, United States of America
| | - Peter A. Tass
- Department of Neurosurgery, Stanford University, Stanford, California, United States of America
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19
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Mushtaq M, Zineldeen DH, Mateen MA, Haider KH. Mesenchymal stem cells' "garbage bags" at work: Treating radial nerve injury with mesenchymal stem cell-derived exosomes. World J Stem Cells 2024; 16:467-478. [PMID: 38817330 PMCID: PMC11135253 DOI: 10.4252/wjsc.v16.i5.467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 04/03/2024] [Accepted: 04/25/2024] [Indexed: 05/24/2024] Open
Abstract
Unlike central nervous system injuries, peripheral nerve injuries (PNIs) are often characterized by more or less successful axonal regeneration. However, structural and functional recovery is a senile process involving multifaceted cellular and molecular processes. The contemporary treatment options are limited, with surgical intervention as the gold-standard method; however, each treatment option has its associated limitations, especially when the injury is severe with a large gap. Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI. The recent pilot study is a leap forward in the field, which is expected to pave the way for more enormous, systematic, and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach, in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.
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Affiliation(s)
- Mazhar Mushtaq
- Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia
| | - Doaa Hussein Zineldeen
- Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta 6632110, Egypt
| | - Muhammad Abdul Mateen
- Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia
| | - Khawaja Husnain Haider
- Department of Basic Sciences, Sulaiman AlRajhi University, Albukairiyah 52736, AlQaseem, Saudi Arabia.
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20
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Li Y, Yang B, Wang Y, Huang Z, Wang J, Pu X, Wen J, Ao Q, Xiao K, Wu J, Yin G. Postoperatively Noninvasive Optogenetic Stimulation via Upconversion Nanoparticles Enhancing Sciatic Nerve Repair. NANO LETTERS 2024; 24:5403-5412. [PMID: 38669639 DOI: 10.1021/acs.nanolett.3c04619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/28/2024]
Abstract
The efficacy of electrical stimulation facilitating peripheral nerve regeneration is evidenced extensively, while the associated secondary damage resulting from repeated electrode invasion and indiscriminate stimulation is inevitable. Here, we present an optogenetics strategy that utilizes upconversion nanoparticles (UCNPs) to convert deeply penetrating near-infrared excitation into blue emission, which activates an adeno-associated virus-encoding ChR2 photoresponsive ion channel on cell membranes. The induced Ca2+ flux, similar to the ion flux in the electrical stimulation approach, efficiently regulates viability and proliferation, secretion of nerve growth factor, and neural function of RSC96 cells. Furthermore, deep near-infrared excitation is harnessed to stimulate autologous Schwann cells in situ via a UCNP-composited scaffold, which enhances nerve sprouting and myelination, consequently promoting functional recovery, electrophysiological restoration, and reinnervation of damaged nerves. This developed postoperatively noninvasive optogenetics strategy presents a novel, minimally traumatic, and enduring therapeutic stimulus to effectively promote peripheral nerve repair.
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Affiliation(s)
- Ya Li
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
- Institute of Regulatory Science for Medical Devices, Sichuan University, Chengdu 610065, China
| | - Bing Yang
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
- Precision Medicine Research Center of West China Hospital, Sichuan University, Chengdu 610093, China
| | - Yulin Wang
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
- Institute of Regulatory Science for Medical Devices, Sichuan University, Chengdu 610065, China
| | - Zhongbing Huang
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
| | - Juan Wang
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
| | - Ximing Pu
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
| | - Jirui Wen
- Department of Otolaryngology Head and Neck Surgery/Deep Underground Space Medical Center West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu 610041, China
| | - Qiang Ao
- Institute of Regulatory Science for Medical Devices, Sichuan University, Chengdu 610065, China
| | - Kai Xiao
- Precision Medicine Research Center of West China Hospital, Sichuan University, Chengdu 610093, China
| | - Jiang Wu
- Department of Otolaryngology Head and Neck Surgery/Deep Underground Space Medical Center West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu 610041, China
| | - Guangfu Yin
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
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21
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Dell'Apa D, Auletta L, Okonji S, Cauduro A, Dondi M, Opreni M, Gandini G, Bianchi E. Traumatic and iatrogenic sciatic nerve injury in 38 dogs and 10 cats: Clinical and electrodiagnostic findings. J Vet Intern Med 2024; 38:1626-1638. [PMID: 38634245 PMCID: PMC11099794 DOI: 10.1111/jvim.17076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 04/01/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Reports describing sciatic nerve injuries (SNI) and their outcome are scarce in veterinary medicine. HYPOTHESIS Describe the causes of traumatic and iatrogenic SNI and evaluate which clinical and electrodiagnostic findings predict outcome. ANIMALS Thirty-eight dogs and 10 cats with confirmed SNI referred for neurologic and electrodiagnostic evaluation. METHODS Clinical and electrodiagnostic examination results, including electromyography (EMG), motor nerve conduction studies, muscle-evoked potential (MEP), F-waves, sensory nerve conduction studies, and cord dorsum potential (CDP), were retrospectively evaluated. Quality of life (QoL) was assessed based on owner interviews. RESULTS Surgery (42%) and trauma (33%) were the most common causes of SNI; in dogs, 24% were caused by bites from wild boars. Ability to flex and extend the tarsus was significantly associated with positive outcome in dogs. Mean time from onset of clinical signs until electrodiagnostic evaluation was 67 ± 65 (range, 7-300) days and 65 ± 108 (range, 7-365) days for dogs and cats, respectively. A cut-off amplitude of 1.45 mV for compound motor action potentials (CMAP) was predictive of positive outcome in dogs (P = .01), with sensitivity of 58% and specificity of 100%. CONCLUSIONS AND CLINICAL IMPORTANCE Clinical motor function predicts recovery better than sensory function. Electrodiagnostic findings also may play a role in predicting the outcome of SNI. Application of the proposed CMAP cut-off amplitude may assist clinicians in shortening the time to reassessment or for earlier suggestion of salvage procedures. Owners perceived a good quality of life (QoL), even in cases of hindlimb amputation.
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Affiliation(s)
| | - Luigi Auletta
- Department of Veterinary Medicine and Animal Sciences (DIVAS)University of MilanMilanItaly
| | - Samuel Okonji
- Department of Veterinary Medical ScienceUniversity of BolognaBolognaItaly
| | | | - Maurizio Dondi
- Department of Veterinary ScienceUniversity of ParmaParmaItaly
| | | | - Gualtiero Gandini
- Department of Veterinary Medical ScienceUniversity of BolognaBolognaItaly
| | - Ezio Bianchi
- Department of Veterinary ScienceUniversity of ParmaParmaItaly
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22
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You Y, Jiang J, Zheng G, Chen Z, Zhu YX, Ma H, Lin H, Guo X, Shi J. In Situ Piezoelectric-Catalytic Anti-Inflammation Promotes the Rehabilitation of Acute Spinal Cord Injury in Synergy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2311429. [PMID: 38298173 DOI: 10.1002/adma.202311429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/21/2023] [Indexed: 02/02/2024]
Abstract
Relieving inflammation via scavenging toxic reactive oxygen species (ROS) during the acute phase of spinal cord injury (SCI) proves to be an effective strategy to mitigate secondary spinal cord injury and improve recovery of motor function. However, commonly used corticosteroid anti-inflammatory drugs show adverse side effects which may induce increased risk of wound infection. Fortunately, hydrogen (H2), featuring selective antioxidant performance, easy penetrability, and excellent biosafety, is being extensively investigated as a potential anti-inflammatory therapeutic gas for the treatment of SCI. In this work, by a facile in situ growth approach of gold nanoparticles (AuNPs) on the piezoelectric BaTiO3, a particulate nanocomposite with Schottky heterojunction (Au@BT) is synthesized, which can generate H2 continuously by catalyzing H+ reduction through piezoelectric catalysis. Further, theoretical calculations are employed to reveal the piezoelectric catalytic mechanism of Au@BT. Transcriptomics analysis and nontargeted large-scale metabolomic analysis reveal the deeper mechanism of the neuroprotective effect of H2 therapy. The as-prepared Au@BT nanoparticle is first explored as a flexible hydrogen gas generator for efficient SCI therapy. This study highlights a promising prospect of nanocatalytic medicine for disease treatments by catalyzing H2 generation; thus, offering a significant alternative to conventional approaches against refractory spinal cord injury.
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Affiliation(s)
- Yanling You
- State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Junjie Jiang
- Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200052, P. R. China
| | - Gang Zheng
- Department of Orthopedics, Shanghai Changzheng Hospital, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, P. R. China
| | - Zhixin Chen
- State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Ya-Xuan Zhu
- Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200331, P. R. China
| | - Hongshi Ma
- State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, P. R. China
| | - Han Lin
- State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
- Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200331, P. R. China
| | - Xiang Guo
- Department of Orthopedics, Shanghai Changzheng Hospital, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, P. R. China
| | - Jianlin Shi
- State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
- Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200331, P. R. China
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23
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Vecchi JT, Rhomberg M, Guymon CA, Hansen MR. The geometry of photopolymerized topography influences neurite pathfinding by directing growth cone morphology and migration. J Neural Eng 2024; 21:026027. [PMID: 38547528 PMCID: PMC10993768 DOI: 10.1088/1741-2552/ad38dc] [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: 09/20/2023] [Revised: 03/15/2024] [Accepted: 03/28/2024] [Indexed: 04/05/2024]
Abstract
Objective. Cochlear implants provide auditory perception to those with severe to profound sensorineural hearing loss: however, the quality of sound perceived by users does not approximate natural hearing. This limitation is due in part to the large physical gap between the stimulating electrodes and their target neurons. Therefore, directing the controlled outgrowth of processes from spiral ganglion neurons (SGNs) into close proximity to the electrode array could provide significantly increased hearing function.Approach.For this objective to be properly designed and implemented, the ability and limits of SGN neurites to be guided must first be determined. In this work, we engineer precise topographical microfeatures with angle turn challenges of various geometries to study SGN pathfinding and use live imaging to better understand how neurite growth is guided by these cues.Main Results.We find that the geometry of the angled microfeatures determines the ability of neurites to navigate the angled microfeature turns. SGN neurite pathfinding fidelity is increased by 20%-70% through minor increases in microfeature amplitude (depth) and by 25% if the angle of the patterned turn is made obtuse. Further, we see that dorsal root ganglion neuron growth cones change their morphology and migration to become more elongated within microfeatures. Our observations also indicate complexities in studying neurite turning. First, as the growth cone pathfinds in response to the various cues, the associated neurite often reorients across the angle topographical microfeatures. Additionally, neurite branching is observed in response to topographical guidance cues, most frequently when turning decisions are most uncertain.Significance.Overall, the multi-angle channel micropatterned substrate is a versatile and efficient system to assess neurite turning and pathfinding in response to topographical cues. These findings represent fundamental principles of neurite pathfinding that will be essential to consider for the design of 3D systems aiming to guide neurite growthin vivo.
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Affiliation(s)
- Joseph T Vecchi
- Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States of America
- Department of Otolaryngology Head-Neck Surgery, University of Iowa, Iowa City, IA, United States of America
| | - Madeline Rhomberg
- Department of Otolaryngology Head-Neck Surgery, University of Iowa, Iowa City, IA, United States of America
| | - C Allan Guymon
- Department of Chemical and Biochemical Engineering, University of Iowa, Iowa City, IA, United States of America
| | - Marlan R Hansen
- Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States of America
- Department of Otolaryngology Head-Neck Surgery, University of Iowa, Iowa City, IA, United States of America
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24
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Alvites R, Lopes B, Coelho A, Maurício AC. Peripheral nerve regeneration: a challenge far from being overcome. Regen Med 2024; 19:155-159. [PMID: 37786972 DOI: 10.2217/rme-2023-0072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2023] Open
Affiliation(s)
- Rui Alvites
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal
- Associate Laboratory for Animal & Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
- Instituto Universitário de Ciências da Saúde (CESPU), Avenida Central de Gandra 1317, Gandra, 4585-116 Paredes, Portugal
| | - Bruna Lopes
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal
- Associate Laboratory for Animal & Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - André Coelho
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal
- Associate Laboratory for Animal & Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
| | - Ana Colette Maurício
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, No. 228, 4050-313 Porto, Portugal
- Associate Laboratory for Animal & Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal
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25
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Jiang M, Chen M, Liu N. Interactions between Schwann cell and extracellular matrix in peripheral nerve regeneration. Front Neurol 2024; 15:1372168. [PMID: 38651098 PMCID: PMC11034552 DOI: 10.3389/fneur.2024.1372168] [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: 01/17/2024] [Accepted: 02/27/2024] [Indexed: 04/25/2024] Open
Abstract
Peripheral nerve injuries, caused by various reasons, often lead to severe sensory, motor, and autonomic dysfunction or permanent disability, posing a challenging problem in regenerative medicine. Autologous nerve transplantation has been the gold standard in traditional treatments but faces numerous limitations and risk factors, such as donor area denervation, increased surgical complications, and diameter or nerve bundle mismatches. The extracellular matrix (ECM) is a complex molecular network synthesized and released into the extracellular space by cells residing in tissues or organs. Its main components include collagen, proteoglycans/glycosaminoglycans, elastin, laminin, fibronectin, etc., providing structural and biochemical support to surrounding cells, crucial for cell survival and growth. Schwann cells, as the primary glial cells in the peripheral nervous system, play various important roles. Schwann cell transplantation is considered the gold standard in cell therapy for peripheral nerve injuries, making ECM derived from Schwann cells one of the most suitable biomaterials for peripheral nerve repair. To better understand the mechanisms of Schwann cells and the ECM in peripheral nerve regeneration and their optimal application, this review provides an overview of their roles in peripheral nerve regeneration.
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Affiliation(s)
- Maorong Jiang
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
| | - Muyang Chen
- School of Life Sciences, Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
| | - Nana Liu
- School of Pediatrics, Nanjing Medical University, Nanjing, China
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26
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Izhiman Y, Esfandiari L. Emerging role of extracellular vesicles and exogenous stimuli in molecular mechanisms of peripheral nerve regeneration. Front Cell Neurosci 2024; 18:1368630. [PMID: 38572074 PMCID: PMC10989355 DOI: 10.3389/fncel.2024.1368630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 02/29/2024] [Indexed: 04/05/2024] Open
Abstract
Peripheral nerve injuries lead to significant morbidity and adversely affect quality of life. The peripheral nervous system harbors the unique trait of autonomous regeneration; however, achieving successful regeneration remains uncertain. Research continues to augment and expedite successful peripheral nerve recovery, offering promising strategies for promoting peripheral nerve regeneration (PNR). These include leveraging extracellular vesicle (EV) communication and harnessing cellular activation through electrical and mechanical stimulation. Small extracellular vesicles (sEVs), 30-150 nm in diameter, play a pivotal role in regulating intercellular communication within the regenerative cascade, specifically among nerve cells, Schwann cells, macrophages, and fibroblasts. Furthermore, the utilization of exogenous stimuli, including electrical stimulation (ES), ultrasound stimulation (US), and extracorporeal shock wave therapy (ESWT), offers remarkable advantages in accelerating and augmenting PNR. Moreover, the application of mechanical and electrical stimuli can potentially affect the biogenesis and secretion of sEVs, consequently leading to potential improvements in PNR. In this review article, we comprehensively delve into the intricacies of cell-to-cell communication facilitated by sEVs and the key regulatory signaling pathways governing PNR. Additionally, we investigated the broad-ranging impacts of ES, US, and ESWT on PNR.
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Affiliation(s)
- Yara Izhiman
- Esfandiari Laboratory, Department of Biomedical Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, OH, United States
| | - Leyla Esfandiari
- Esfandiari Laboratory, Department of Biomedical Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, OH, United States
- Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
- Department of Electrical and Computer Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, OH, United States
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27
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Albin B, Adhikari P, Tiwari AP, Qubbaj K, Yang IH. Electrical stimulation enhances mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathy. iScience 2024; 27:109052. [PMID: 38375222 PMCID: PMC10875116 DOI: 10.1016/j.isci.2024.109052] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/20/2023] [Accepted: 01/23/2024] [Indexed: 02/21/2024] Open
Abstract
Electrical stimulation (ESTIM) has shown to be an effective symptomatic treatment to treat pain associated with peripheral nerve damage. However, the neuroprotective mechanism of ESTIM on peripheral neuropathies is still unknown. In this study, we identified that ESTIM has the ability to enhance mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathies (CIPNs). CIPN is a debilitating and painful sequalae of anti-cancer chemotherapy treatment which results in degeneration of peripheral nerves. Mitochondrial dynamics were analyzed within axons in response to two different antineoplastic mechanisms by chemotherapy drug treatments paclitaxel and oxaliplatin in vitro. Mitochondrial trafficking response to chemotherapy drug treatment was observed to decrease in conjunction with degeneration of distal axons. Using low-frequency ESTIM, we observed enhanced mitochondrial trafficking to be a neuroprotective mechanism against CIPN. This study confirms ESTIM enhances regeneration of peripheral nerves by increased mitochondrial trafficking.
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Affiliation(s)
- Bayne Albin
- Center for Biomedical Engineering and Science, Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
| | - Prashant Adhikari
- Center for Biomedical Engineering and Science, Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
| | - Arjun Prasad Tiwari
- Center for Biomedical Engineering and Science, Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
| | - Khayzaran Qubbaj
- Center for Biomedical Engineering and Science, Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
| | - In Hong Yang
- Center for Biomedical Engineering and Science, Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
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28
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Gusev E, Sarapultsev A. Interplay of G-proteins and Serotonin in the Neuroimmunoinflammatory Model of Chronic Stress and Depression: A Narrative Review. Curr Pharm Des 2024; 30:180-214. [PMID: 38151838 DOI: 10.2174/0113816128285578231218102020] [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: 10/04/2023] [Accepted: 11/29/2023] [Indexed: 12/29/2023]
Abstract
INTRODUCTION This narrative review addresses the clinical challenges in stress-related disorders such as depression, focusing on the interplay between neuron-specific and pro-inflammatory mechanisms at the cellular, cerebral, and systemic levels. OBJECTIVE We aim to elucidate the molecular mechanisms linking chronic psychological stress with low-grade neuroinflammation in key brain regions, particularly focusing on the roles of G proteins and serotonin (5-HT) receptors. METHODS This comprehensive review of the literature employs systematic, narrative, and scoping review methodologies, combined with systemic approaches to general pathology. It synthesizes current research on shared signaling pathways involved in stress responses and neuroinflammation, including calcium-dependent mechanisms, mitogen-activated protein kinases, and key transcription factors like NF-κB and p53. The review also focuses on the role of G protein-coupled neurotransmitter receptors (GPCRs) in immune and pro-inflammatory responses, with a detailed analysis of how 13 of 14 types of human 5-HT receptors contribute to depression and neuroinflammation. RESULTS The review reveals a complex interaction between neurotransmitter signals and immunoinflammatory responses in stress-related pathologies. It highlights the role of GPCRs and canonical inflammatory mediators in influencing both pathological and physiological processes in nervous tissue. CONCLUSION The proposed Neuroimmunoinflammatory Stress Model (NIIS Model) suggests that proinflammatory signaling pathways, mediated by metabotropic and ionotropic neurotransmitter receptors, are crucial for maintaining neuronal homeostasis. Chronic mental stress can disrupt this balance, leading to increased pro-inflammatory states in the brain and contributing to neuropsychiatric and psychosomatic disorders, including depression. This model integrates traditional theories on depression pathogenesis, offering a comprehensive understanding of the multifaceted nature of the condition.
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Affiliation(s)
- Evgenii Gusev
- Laboratory of Inflammation Immunology, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, Ekaterinburg 620049, Russia
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, Chelyabinsk 454080, Russia
| | - Alexey Sarapultsev
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, Chelyabinsk 454080, Russia
- Laboratory of Immunopathophysiology, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, Ekaterinburg 620049, Russia
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29
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Zueva MV, Neroeva NV, Zhuravleva AN, Bogolepova AN, Kotelin VV, Fadeev DV, Tsapenko IV. Fractal Phototherapy in Maximizing Retina and Brain Plasticity. ADVANCES IN NEUROBIOLOGY 2024; 36:585-637. [PMID: 38468055 DOI: 10.1007/978-3-031-47606-8_31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/13/2024]
Abstract
The neuroplasticity potential is reduced with aging and impairs during neurodegenerative diseases and brain and visual system injuries. This limits the brain's capacity to repair the structure and dynamics of its activity after lesions. Maximization of neuroplasticity is necessary to provide the maximal CNS response to therapeutic intervention and adaptive reorganization of neuronal networks in patients with degenerative pathology and traumatic injury to restore the functional activity of the brain and retina.Considering the fractal geometry and dynamics of the healthy brain and the loss of fractality in neurodegenerative pathology, we suggest that the application of self-similar visual signals with a fractal temporal structure in the stimulation therapy can reactivate the adaptive neuroplasticity and enhance the effectiveness of neurorehabilitation. This proposition was tested in the recent studies. Patients with glaucoma had a statistically significant positive effect of fractal photic therapy on light sensitivity and the perimetric MD index, which shows that methods of fractal stimulation can be a novel nonpharmacological approach to neuroprotective therapy and neurorehabilitation. In healthy rabbits, it was demonstrated that a long-term course of photostimulation with fractal signals does not harm the electroretinogram (ERG) and retina structure. Rabbits with modeled retinal atrophy showed better dynamics of the ERG restoration during daily stimulation therapy for a week in comparison with the controls. Positive changes in the retinal function can indirectly suggest the activation of its adaptive plasticity and the high potential of stimulation therapy with fractal visual stimuli in a nonpharmacological neurorehabilitation, which requires further study.
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Affiliation(s)
- Marina V Zueva
- Department of Clinical Physiology of Vision, Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - Natalia V Neroeva
- Department of Pathology of the Retina and Optic Nerve, Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - Anastasia N Zhuravleva
- Department of Glaucoma, Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - Anna N Bogolepova
- Department of neurology, neurosurgery and medical genetics, Pirogov Russian National Research Medical University, Moscow, Russia
| | - Vladislav V Kotelin
- Department of Clinical Physiology of Vision, Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - Denis V Fadeev
- Scientific Experimental Center Department, Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
| | - Irina V Tsapenko
- Department of Clinical Physiology of Vision, Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia
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30
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Wasnik K, Gupta PS, Mukherjee S, Oviya A, Prakash R, Pareek D, Patra S, Maity S, Rai V, Singh M, Singh G, Yadav DD, Das S, Maiti P, Paik P. Poly( N-acryloylglycine-acrylamide) Hydrogel Mimics the Cellular Microenvironment and Promotes Neurite Growth with Protection from Oxidative Stress. ACS APPLIED BIO MATERIALS 2023; 6:5644-5661. [PMID: 37993284 DOI: 10.1021/acsabm.3c00807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2023]
Abstract
In this work, the glycine-based acryloyl monomer is polymerized to obtain a neurogenic polymeric hydrogel for regenerative applications. The synthesized poly(N-acryloylglycine-acrylamide) [poly(NAG-b-A)] nanohydrogel exhibits high swelling (∼1500%) and is mechanically very stable, biocompatible, and proliferative in nature. The poly(NAG-b-A) nanohydrogel provides a stable 3D extracellular mimetic environment and promotes healthy neurite growth for primary cortical neurons by facilitating cellular adhesion, proliferation, actin filament stabilization, and neuronal differentiation. Furthermore, the protective role of the poly(NAG-b-A) hydrogel for the neurons in oxidative stress conditions is revealed and it is found that it is a clinically relevant material for neuronal regenerative applications, such as for promoting nerve regeneration via GSK3β inhibition. This hydrogel additionally plays an important role in modulating the biological microenvironment, either as an agonist and antagonist or as an antioxidant. Furthermore, it favors the physiological responses and eases the neurite growth efficiency. Additionally, we found out that the conversion of glycine-based acryloyl monomers into their corresponding polymer modulates the mechanical performance, mimics the cellular microenvironment, and accelerates the self-healing capability due to the responsive behavior towards reactive oxygen species (ROS). Thus, the p(NAG-b-A) hydrogel could be a potential candidate to induce neuronal regeneration since it provides a physical cue and significantly boosts neurite outgrowth and also maintains the microtubule integrity in neuronal cells.
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Affiliation(s)
- Kirti Wasnik
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Prem Shankar Gupta
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Sudip Mukherjee
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Alagu Oviya
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Ravi Prakash
- School of Material Science, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Divya Pareek
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Sukanya Patra
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Somedutta Maity
- School of Engineering Sciences and Technology, University of Hyderabad, Hyderabad, Telangana State 500 046, India
| | - Vipin Rai
- Department of Biochemistry, Institute of Sciences, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Monika Singh
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Gurmeet Singh
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Desh Deepak Yadav
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Santanu Das
- Department of Ceramic Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Pralay Maiti
- School of Material Science, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
| | - Pradip Paik
- School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh 221 005, India
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Vincent PF, Young ED, Edge AS, Glowatzki E. Auditory Hair Cells and Spiral Ganglion Neurons Regenerate Synapses with Refined Release Properties In Vitro. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.05.561095. [PMID: 38076928 PMCID: PMC10705289 DOI: 10.1101/2023.10.05.561095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2023]
Abstract
Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing 'synaptopathy 'and hearing loss. Co-cultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings, showing that newly formed IHC synapses are indeed functional, exhibiting glutamatergic excitatory postsynaptic currents. When older organs of Corti were plated, synaptic activity probed by deconvolution, showed more mature release properties, closer to the highly specialized mode of IHC synaptic transmission that is crucial for coding the sound signal. This newly developed functional assessment of regenerated IHC synapses provides a powerful tool for testing approaches to improve synapse regeneration.
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Affiliation(s)
- Philippe F.Y. Vincent
- The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Eric D. Young
- The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Biomedical Engineering, The Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Albert S.B. Edge
- Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA
- Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA
- Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, Massachusetts, USA
- Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
| | - Elisabeth Glowatzki
- The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, Maryland
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Shi S, Ou X, Cheng D. How Advancing is Peripheral Nerve Regeneration Using Nanofiber Scaffolds? A Comprehensive Review of the Literature. Int J Nanomedicine 2023; 18:6763-6779. [PMID: 38026517 PMCID: PMC10657550 DOI: 10.2147/ijn.s436871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/02/2023] [Indexed: 12/01/2023] Open
Abstract
Peripheral nerve injuries present significant challenges in regenerative medicine, primarily due to inherent limitations in the body's natural healing processes. In response to these challenges and with the aim of enhancing peripheral nerve regeneration, nanofiber scaffolds have emerged as a promising and advanced intervention. However, a deeper understanding of the underlying mechanistic foundations that drive the favorable contributions of nanofiber scaffolds to nerve regeneration is essential. In this comprehensive review, we make an exploration of the latent potential of nanofiber scaffolds in augmenting peripheral nerve regeneration. This exploration includes a detailed introduction to the fabrication methods of nanofibers, an analysis of the intricate interactions between these scaffolds and cellular entities, an examination of strategies related to the controlled release of bioactive agents, an assessment of the prospects for clinical translation, an exploration of emerging trends, and thorough considerations regarding biocompatibility and safety. By comprehensively elucidating the intricate structural attributes and multifaceted functional capacities inherent in nanofiber scaffolds, we aim to offer a prospective and effective strategy for the treatment of peripheral nerve injury.
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Affiliation(s)
- Shaoyan Shi
- Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an Honghui Hospital North District, Xi’an, Shaanxi, 710000, People’s Republic of China
| | - Xuehai Ou
- Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an Honghui Hospital North District, Xi’an, Shaanxi, 710000, People’s Republic of China
| | - Deliang Cheng
- Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an Honghui Hospital North District, Xi’an, Shaanxi, 710000, People’s Republic of China
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Sarapultsev A, Gusev E, Komelkova M, Utepova I, Luo S, Hu D. JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions. MOLECULAR BIOMEDICINE 2023; 4:40. [PMID: 37938494 PMCID: PMC10632324 DOI: 10.1186/s43556-023-00151-1] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 10/26/2023] [Indexed: 11/09/2023] Open
Abstract
The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological and pathological processes such as inflammation and stress. Dysregulation in this pathway can lead to severe immunodeficiencies and malignancies, and its role extends to neurotransduction and pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological and inflammatory disorders, their application has generally been limited to diseases with similar pathogenic features. Despite the modest expression of JAK-STAT in the CNS, it is crucial for functions in the cortex, hippocampus, and cerebellum, making it relevant in conditions like Parkinson's disease and other neuroinflammatory disorders. Furthermore, the influence of the pathway on serotonin receptors and phospholipase C has implications for stress and mood disorders. This review expands the understanding of JAK-STAT, moving beyond traditional immunological contexts to explore its role in stress-related disorders and CNS function. Recent findings, such as the effectiveness of Jakinibs in chronic conditions such as rheumatoid arthritis, expand their therapeutic applicability. Advances in isoform-specific inhibitors, including filgotinib and upadacitinib, promise greater specificity with fewer off-target effects. Combination therapies, involving Jakinibs and monoclonal antibodies, aiming to enhance therapeutic specificity and efficacy also give great hope. Overall, this review bridges the gap between basic science and clinical application, elucidating the complex influence of the JAK-STAT pathway on human health and guiding future interventions.
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Affiliation(s)
- Alexey Sarapultsev
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 454080, Chelyabinsk, Russia.
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049, Ekaterinburg, Russia.
| | - Evgenii Gusev
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 454080, Chelyabinsk, Russia
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049, Ekaterinburg, Russia
| | - Maria Komelkova
- Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 454080, Chelyabinsk, Russia
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049, Ekaterinburg, Russia
| | - Irina Utepova
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049, Ekaterinburg, Russia
- Department of Organic and Biomolecular Chemistry, Ural Federal University, 620002, Ekaterinburg, Russian Federation
| | - Shanshan Luo
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Desheng Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Key Laboratory of Biological Targeted Therapy, The Ministry of Education, Wuhan, 430022, China
- Clinical Research Center of Cancer Immunotherapy, Hubei Wuhan, 430022, China
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Štepánková K, Chudíčková M, Šimková Z, Martinez-Varea N, Kubinová Š, Urdzíková LM, Jendelová P, Kwok JCF. Low oral dose of 4-methylumbelliferone reduces glial scar but is insufficient to induce functional recovery after spinal cord injury. Sci Rep 2023; 13:19183. [PMID: 37932336 PMCID: PMC10628150 DOI: 10.1038/s41598-023-46539-5] [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: 07/16/2023] [Accepted: 11/02/2023] [Indexed: 11/08/2023] Open
Abstract
Spinal cord injury (SCI) induces the upregulation of chondroitin sulfate proteoglycans (CSPGs) at the glial scar and inhibits neuroregeneration. Under normal physiological condition, CSPGs interact with hyaluronan (HA) and other extracellular matrix on the neuronal surface forming a macromolecular structure called perineuronal nets (PNNs) which regulate neuroplasticity. 4-methylumbelliferone (4-MU) is a known inhibitor for HA synthesis but has not been tested in SCI. We first tested the effect of 4-MU in HA reduction in uninjured rats. After 8 weeks of 4-MU administration at a dose of 1.2 g/kg/day, we have not only observed a reduction of HA in the uninjured spinal cords but also a down-regulation of CS glycosaminoglycans (CS-GAGs). In order to assess the effect of 4-MU in chronic SCI, six weeks after Th8 spinal contusion injury, rats were fed with 4-MU or placebo for 8 weeks in combination with daily treadmill rehabilitation for 16 weeks to promote neuroplasticity. 4-MU treatment reduced the HA synthesis by astrocytes around the lesion site and increased sprouting of 5-hydroxytryptamine fibres into ventral horns. However, the current dose was not sufficient to suppress CS-GAG up-regulation induced by SCI. Further adjustment on the dosage will be required to benefit functional recovery after SCI.
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Affiliation(s)
- Kateřina Štepánková
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic.
- Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006, Prague, Czech Republic.
| | - Milada Chudíčková
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic
| | - Zuzana Šimková
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic
| | - Noelia Martinez-Varea
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic
- Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006, Prague, Czech Republic
| | - Šárka Kubinová
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic
- Institute of Physics, Czech Academy of Sciences, 182 21, Prague, Czech Republic
| | - Lucia Machová Urdzíková
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic.
- Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006, Prague, Czech Republic.
| | - Pavla Jendelová
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic.
- Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006, Prague, Czech Republic.
| | - Jessica C F Kwok
- Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská, 1083, Prague, Czech Republic.
- Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
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Javidi H, Ramazani Saadatabadi A, Sadrnezhaad SK, Najmoddin N. Conductive nerve conduit with piezoelectric properties for enhanced PC12 differentiation. Sci Rep 2023; 13:12004. [PMID: 37491480 PMCID: PMC10368663 DOI: 10.1038/s41598-023-38456-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 07/08/2023] [Indexed: 07/27/2023] Open
Abstract
Restoration of nerve tissue remains highly challenging, mainly due to the limited regeneration capacity of the nervous system and the development of fibrosis. This limitation necessitates designing new nerve guidance channel to promote nerve repairing. In this study, we developed a novel core/shell conduit to induce PC12 differentiation. Co-electrospinning method was utilized to produce a fibrous shell containing polycaprolactone/polyvinylidene fluoride PCL/PVDF, gelatin and polyaniline/graphene (PAG) nanocomposite. The core section of the conduit was filled with chitosan-gelatin hydrogel containing PAG and ZnO nanoparticles. Such conduit shows antibacterial activity, electrical conductivity and piezoelectric property. The effect of such engineered conduit on PC12 differentiation was investigated by analyzing differentiation markers Nestin and microtubule-associated protein 2 (MAP2) through immunocytochemistry and PCR-RT techniques. The result revealed that such conduit could significantly induce Nestin and MAP2 gene expression in the PC12 cells and, thus, it is a viable option for effective cell differentiation and nerve regeneration.
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Affiliation(s)
- Hamideh Javidi
- Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - S K Sadrnezhaad
- Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran
| | - Najmeh Najmoddin
- Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.
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Coyoy-Salgado A, Orozco-Barrios C, Sánchez-Torres S, Olayo MG, Cruz GJ, Morales-Corona J, Olayo R, Diaz-Ruiz A, Ríos C, Alvarez-Mejia L, Mondragón-Lozano R, Morales-Guadarrama A, Alonso-García AL, Fabela-Sánchez O, Salgado-Ceballos H. Gene expression and locomotor recovery in adult rats with spinal cord injury and plasma-synthesized polypyrrole/iodine application combined with a mixed rehabilitation scheme. Front Neurol 2023; 14:1124245. [PMID: 37288064 PMCID: PMC10243140 DOI: 10.3389/fneur.2023.1124245] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 04/14/2023] [Indexed: 06/09/2023] Open
Abstract
Introduction Spinal cord injury (SCI) can cause paralysis, for which effective therapeutic strategies have not been developed yet. The only accepted strategy for patients is rehabilitation (RB), although this does not allow complete recovery of lost functions, which makes it necessary to combine it with strategies such as plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical properties than PPy synthesized by conventional methods. After SCI in rats, PPy/I promotes functional recovery. Therefore, the purpose of this study was to increase the beneficial effects of both strategies and identify which genes activate PPy/I when applied alone or in combination with a mixed scheme of RB by swimming and enriched environment (SW/EE) in rats with SCI. Methods Microarray analysis was performed to identify mechanisms of action underlying the effects of PPy/I and PPy/I+SW/EE on motor function recovery as evaluated by the BBB scale. Results Results showed robust upregulation by PPy/I in genes related to the developmental process, biogenesis, synapse, and synaptic vesicle trafficking. In addition, PPy/I+SW/EE increased the expression of genes related to proliferation, biogenesis, cell development, morphogenesis, cell differentiation, neurogenesis, neuron development, and synapse formation processes. Immunofluorescence analysis showed the expression of β-III tubulin in all groups, a decreased expression of caspase-3 in the PPy/I group and GFAP in the PPy/I+SW/EE group (p < 0.05). Better preservation of nerve tissue was observed in PPy/I and PPy/SW/EE groups (p < 0.05). In the BBB scale, the control group scored 1.72 ± 0.41, animals with PPy/I treatment scored 4.23 ± 0.33, and those with PPy/I+SW/EE scored 9.13 ± 0.43 1 month after follow-up. Conclusion Thus, PPy/I+SW/EE could represent a therapeutic alternative for motor function recovery after SCI.
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Affiliation(s)
- Angélica Coyoy-Salgado
- Researchers for Mexico CONACyT-Instituto Mexicano del Seguro Social, Medical Research Unit in Neurological Diseases, Specialty Hospital, National Medical Center Siglo XXI, Mexico City, Mexico
- Research Center of the Proyecto CAMINA A.C., Mexico City, Mexico
| | - Carlos Orozco-Barrios
- Researchers for Mexico CONACyT-Instituto Mexicano del Seguro Social, Medical Research Unit in Neurological Diseases, Specialty Hospital, National Medical Center Siglo XXI, Mexico City, Mexico
- Research Center of the Proyecto CAMINA A.C., Mexico City, Mexico
| | - Stephanie Sánchez-Torres
- Research Center of the Proyecto CAMINA A.C., Mexico City, Mexico
- Instituto Mexicano del Seguro Social, Medical Research Unit in Neurological Diseases, Specialty Hospital, National Medical Center Siglo XXI, Mexico City, Mexico
| | - María Guadalupe Olayo
- Instituto Nacional de Investigaciones Nucleares, Department of Physics, Axapusco, Mexico
| | - Guillermo Jesus Cruz
- Instituto Nacional de Investigaciones Nucleares, Department of Physics, Axapusco, Mexico
| | - Juan Morales-Corona
- Department of Physics, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico
| | - Roberto Olayo
- Department of Physics, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico
| | - Araceli Diaz-Ruiz
- Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., Department of Neurochemistry, Mexico City, Mexico
| | - Camilo Ríos
- Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., Department of Neurochemistry, Mexico City, Mexico
| | - Laura Alvarez-Mejia
- Research Center of the Proyecto CAMINA A.C., Mexico City, Mexico
- Instituto Mexicano del Seguro Social, Medical Research Unit in Neurological Diseases, Specialty Hospital, National Medical Center Siglo XXI, Mexico City, Mexico
| | - Rodrigo Mondragón-Lozano
- Researchers for Mexico CONACyT-Instituto Mexicano del Seguro Social, Medical Research Unit in Neurological Diseases, Specialty Hospital, National Medical Center Siglo XXI, Mexico City, Mexico
- Research Center of the Proyecto CAMINA A.C., Mexico City, Mexico
| | - Axayacatl Morales-Guadarrama
- Electrical Engineering Department, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico
- National Center for Research in Imaging and Medical Instrumentation, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico
| | | | - Omar Fabela-Sánchez
- Researchers for Mexico CONACyT-Centro de Investigación en Química Aplicada, Department of Chemistry Macromolecules and Nanomaterials, Saltillo, Mexico
| | - Hermelinda Salgado-Ceballos
- Research Center of the Proyecto CAMINA A.C., Mexico City, Mexico
- Instituto Mexicano del Seguro Social, Medical Research Unit in Neurological Diseases, Specialty Hospital, National Medical Center Siglo XXI, Mexico City, Mexico
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Bloch A, Shany-Ur T, Sharoni L, Bar-Lev N, Salomon-Shushan T, Maril S, Druckman E, Hoofien D. Time from injury and age interact in relationship with perceived quality of life outcomes following vocation-focused neuropsychological rehabilitation. Front Psychol 2023; 14:1047615. [PMID: 36844267 PMCID: PMC9950548 DOI: 10.3389/fpsyg.2023.1047615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 01/19/2023] [Indexed: 02/12/2023] Open
Abstract
At the group level, community-based neuropsychological rehabilitation interventions with a vocational focus are generally effective among individuals with brain injuries. However, individual participants vary significantly in the extent of their improvement, prompting attempts to elucidate individual, injury-related, and environmental factors affecting prognosis. In this study, we examined the relationships between one such factor - "time from injury" (the time between injury and intervention) - and two outcome measures: employment status and perceived quality of life (PQoL), in 157 brain injury survivors, before and after a holistic neuropsychological vocational rehabilitation program. We also examined whether relationships between the variables were moderated by age at onset of treatment and injury severity. In the entire sample, both the proportion of employed participants and average PQoL increased following program participation. Neither, time from injury, severity, nor age at onset of treatment predicted the increase in employment proportion, and severity was not a significant predictor of PQoL. However, an interactive effect indicated that when treatment was started at a younger age, longer time from injury predicted higher levels of PQoL, but when treatment was started at older ages, longer time from injury predicted lower levels of PQoL. When interpreted alongside existing literature, these results suggest that delaying vocational components of rehabilitation can be beneficial for younger participants, while the effectiveness of vocational rehabilitation can be maximized by starting as early as possible among older participants. Most importantly, regardless of age, it appears that vocational rehabilitation can be effective even when initiated many years after injury.
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Affiliation(s)
- Ayala Bloch
- Department of Psychology, Ariel University, Ariel, Israel,The National Institute of Neuropsychological Rehabilitation, Tel Aviv, Israel,*Correspondence: Ayala Bloch, ✉
| | - Tal Shany-Ur
- The National Institute of Neuropsychological Rehabilitation, Tel Aviv, Israel,Department of Psychology, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Limor Sharoni
- The National Institute of Neuropsychological Rehabilitation, Tel Aviv, Israel
| | - Narkis Bar-Lev
- The National Institute of Neuropsychological Rehabilitation, Tel Aviv, Israel
| | | | - Sari Maril
- The National Institute of Neuropsychological Rehabilitation, Tel Aviv, Israel
| | - Eran Druckman
- Druckman Research and Statistics Lab, Rishon Lezion, Israel
| | - Dan Hoofien
- The National Institute of Neuropsychological Rehabilitation, Tel Aviv, Israel,The School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel
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Wakhloo D, Oberhauser J, Madira A, Mahajani S. From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer's and Parkinson's diseases. Neural Regen Res 2022; 17:2606-2614. [PMID: 35662189 PMCID: PMC9165389 DOI: 10.4103/1673-5374.336138] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/16/2021] [Accepted: 12/02/2021] [Indexed: 11/29/2022] Open
Abstract
Two of the most common neurodegenerative disorders - Alzheimer's and Parkinson's diseases - are characterized by synaptic dysfunction and degeneration that culminate in neuronal loss due to abnormal protein accumulation. The intracellular aggregation of hyper-phosphorylated tau and the extracellular aggregation of amyloid beta plaques form the basis of Alzheimer's disease pathology. The major hallmark of Parkinson's disease is the loss of dopaminergic neurons in the substantia nigra pars compacta, following the formation of Lewy bodies, which consists primarily of alpha-synuclein aggregates. However, the discrete mechanisms that contribute to neurodegeneration in these disorders are still poorly understood. Both neuronal loss and impaired adult neurogenesis have been reported in animal models of these disorders. Yet these findings remain subject to frequent debate due to a lack of conclusive evidence in post mortem brain tissue from human patients. While some publications provide significant findings related to axonal regeneration in Alzheimer's and Parkinson's diseases, they also highlight the limitations and obstacles to the development of neuroregenerative therapies. In this review, we summarize in vitro and in vivo findings related to neurogenesis, neuroregeneration and neurodegeneration in the context of Alzheimer's and Parkinson's diseases.
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Affiliation(s)
- Debia Wakhloo
- Deparment of Neuropathology, Stanford University, School of Medicine, Stanford, CA, USA
| | - Jane Oberhauser
- Deparment of Neuropathology, Stanford University, School of Medicine, Stanford, CA, USA
| | - Angela Madira
- Deparment of Neuropathology, Stanford University, School of Medicine, Stanford, CA, USA
| | - Sameehan Mahajani
- Deparment of Neuropathology, Stanford University, School of Medicine, Stanford, CA, USA
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Leemhuis E, Favieri F, Forte G, Pazzaglia M. Integrated Neuroregenerative Techniques for Plasticity of the Injured Spinal Cord. Biomedicines 2022; 10:biomedicines10102563. [PMID: 36289825 PMCID: PMC9599452 DOI: 10.3390/biomedicines10102563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/18/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
On the slow path to improving the life expectancy and quality of life of patients post spinal cord injury (SCI), recovery remains controversial. The potential role of the regenerative capacity of the nervous system has led to numerous attempts to stimulate the SCI to re-establish the interrupted sensorimotor loop and to understand its potential in the recovery process. Numerous resources are now available, from pharmacological to biomolecular approaches and from neuromodulation to sensorimotor rehabilitation interventions based on the use of various neural interfaces, exoskeletons, and virtual reality applications. The integration of existing resources seems to be a promising field of research, especially from the perspective of improving living conditions in the short to medium term. Goals such as reducing chronic forms of neuropathic pain, regaining control over certain physiological activities, and enhancing residual abilities are often more urgent than complete functional recovery. In this perspective article, we provide an overview of the latest interventions for the treatment of SCI through broad phases of injury rehabilitation. The underlying intention of this work is to introduce a spinal cord neuroplasticity-based multimodal approach to promote functional recovery and improve quality of life after SCI. Nonetheless, when used separately, biomolecular therapeutic approaches have been shown to have modest outcomes.
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Affiliation(s)
- Erik Leemhuis
- Dipartimento di Psicologia, Sapienza Università di Roma, 00185 Rome, Italy
- Body and Action Lab, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy
- Correspondence: (E.L.); (M.P.)
| | - Francesca Favieri
- Dipartimento di Psicologia, Sapienza Università di Roma, 00185 Rome, Italy
- Body and Action Lab, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy
| | - Giuseppe Forte
- Body and Action Lab, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy
- Dipartimento di Psicologia Dinamica, Clinica e Salute, Sapienza Università di Roma, 00185 Roma, Italy
| | - Mariella Pazzaglia
- Dipartimento di Psicologia, Sapienza Università di Roma, 00185 Rome, Italy
- Body and Action Lab, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy
- Correspondence: (E.L.); (M.P.)
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Perspectives on the Molecular Mediators of Oxidative Stress and Antioxidant Strategies in the Context of Neuroprotection and Neurolongevity: An Extensive Review. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:7743705. [PMID: 36062188 PMCID: PMC9439934 DOI: 10.1155/2022/7743705] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/09/2022] [Indexed: 12/11/2022]
Abstract
Molecules with at least one unpaired electron in their outermost shell are known as free radicals. Free radical molecules are produced either within our bodies or by external sources such as ozone, cigarette smoking, X-rays, industrial chemicals, and air pollution. Disruption of normal cellular homeostasis by redox signaling may result in cardiovascular, neurodegenerative diseases and cancer. Although ROS (reactive oxygen species) are formed in the GI tract, little is known about how they contribute to pathophysiology and disease etiology. When reactive oxygen species and antioxidants are in imbalance in our bodies, they can cause cell structure damage, neurodegenerative diseases, diabetes, hypercholesterolemia, atherosclerosis, cancer, cardiovascular diseases, metabolic disorders, and other obesity-related disorders, as well as protein misfolding, mitochondrial dysfunction, glial cell activation, and subsequent cellular apoptosis. Neuron cells are gradually destroyed in neurodegenerative diseases. The production of inappropriately aggregated proteins is strongly linked to oxidative stress. This review's goal is to provide as much information as possible about the numerous neurodegenerative illnesses linked to oxidative stress. The possibilities of multimodal and neuroprotective therapy in human illness, using already accessible medications and demonstrating neuroprotective promise in animal models, are highlighted. Neuroprotection and neurolongevity may improve from the use of bioactive substances from medicinal herbs like Allium stadium, Celastrus paniculatus, and Centella asiatica. Many neuroprotective drugs' possible role has been addressed. Preventing neuroinflammation has been demonstrated in several animal models.
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41
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Tanaka M, Vécsei L. Editorial of Special Issue ‘Dissecting Neurological and Neuropsychiatric Diseases: Neurodegeneration and Neuroprotection’. Int J Mol Sci 2022; 23:ijms23136991. [PMID: 35805990 PMCID: PMC9266548 DOI: 10.3390/ijms23136991] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 06/15/2022] [Indexed: 02/04/2023] Open
Affiliation(s)
- Masaru Tanaka
- ELKH-SZTE Neuroscience Research Group, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Semmelweis u. 6, H-6725 Szeged, Hungary
| | - László Vécsei
- ELKH-SZTE Neuroscience Research Group, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Semmelweis u. 6, H-6725 Szeged, Hungary
- Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
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Seah JJ, Wang DY. Pushing the frontiers of military medical excellence: updates, progress and future needs. Mil Med Res 2022; 9:27. [PMID: 35681166 PMCID: PMC9183759 DOI: 10.1186/s40779-022-00388-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 05/26/2022] [Indexed: 12/25/2022] Open
Abstract
Since its establishment in 2014, Military Medical Research has come a long way in becoming a premier journal for scientific articles from various different specialties, with a special emphasis on topics with military relevance. The field of military medicine may be obscure, and may not be readily encountered by the typical clinician on a day-to-day basis. This journal aims not only to pursue excellence in military research, but also keep current with the latest advancements on general medical topics from each and every specialty. This editorial serves to recap and synthesize the existing progress, updates and future needs of military medical excellence, discussing foremostly the unique traits of literature published in this journal, and subsequently presenting the discourse regarding wartime and peacetime medicine, the role of the military in a public health emergency, as well as wound healing and organ regeneration. Special attention have been devoted to military topics to shed light on the effects of Chemical, Biological, Radiological and Explosive (CBRE) warfare, environmental medicine and military psychiatry, topics which rarely have a chance to be discussed elsewhere. The interconnectedness between military combat and soldier physical and mental well-being is intricate, and has been distorted by pandemics such as coronavirus disease 2019 (COVID-19). This journal has come a long way since its first article was published, steadily contributing to the existing knowledge pool on general medical topics with a military slant. Only with continuous research and sharing, can we build upon the work of the scientific community, with hopes for the betterment of patient care.
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Affiliation(s)
- Jun Jie Seah
- Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - De-Yun Wang
- Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Hausott B, Glueckert R, Schrott-Fischer A, Klimaschewski L. Signal Transduction Regulators in Axonal Regeneration. Cells 2022; 11:cells11091537. [PMID: 35563843 PMCID: PMC9104247 DOI: 10.3390/cells11091537] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/27/2022] [Accepted: 04/28/2022] [Indexed: 11/16/2022] Open
Abstract
Intracellular signal transduction in response to growth factor receptor activation is a fundamental process during the regeneration of the nervous system. In this context, intracellular inhibitors of neuronal growth factor signaling have become of great interest in the recent years. Among them are the prominent signal transduction regulators Sprouty (SPRY) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which interfere with major signaling pathways such as extracellular signal-regulated kinase (ERK) or phosphoinositide 3-kinase (PI3K)/Akt in neurons and glial cells. Furthermore, SPRY and PTEN are themselves tightly regulated by ubiquitin ligases such as c-casitas b-lineage lymphoma (c-CBL) or neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) and by different microRNAs (miRs) including miR-21 and miR-222. SPRY, PTEN and their intracellular regulators play an important role in the developing and the lesioned adult central and peripheral nervous system. This review will focus on the effects of SPRY and PTEN as well as their regulators in various experimental models of axonal regeneration in vitro and in vivo. Targeting these signal transduction regulators in the nervous system holds great promise for the treatment of neurological injuries in the future.
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Affiliation(s)
- Barbara Hausott
- Institute of Neuroanatomy, Medical University Innsbruck, 6020 Innsbruck, Austria;
- Correspondence:
| | - Rudolf Glueckert
- Department of Otorhinolaryngology, Medical University Innsbruck, 6020 Innsbruck, Austria; (R.G.); (A.S.-F.)
| | - Anneliese Schrott-Fischer
- Department of Otorhinolaryngology, Medical University Innsbruck, 6020 Innsbruck, Austria; (R.G.); (A.S.-F.)
| | - Lars Klimaschewski
- Institute of Neuroanatomy, Medical University Innsbruck, 6020 Innsbruck, Austria;
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Role and Impact of Cerebrolysin for Ischemic Stroke Care. J Clin Med 2022; 11:jcm11051273. [PMID: 35268364 PMCID: PMC8911124 DOI: 10.3390/jcm11051273] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/20/2022] [Accepted: 02/23/2022] [Indexed: 01/01/2023] Open
Abstract
Stroke is still a significant health problem that affects millions of people worldwide, as it is the second-leading cause of death and the third-leading cause of disability. Many changes have occurred in the treatment of acute ischemic stroke. Although the innovative concepts of neuroprotection and neurorecovery have been vigorously investigated in a substantial number of clinical studies in the past, only a few trials managed to increase the number of promising outcomes with regard to the multidimensional construct of brain protection and rehabilitation. In terms of pharmacological therapies with proven benefits in the post-ischemic process, drugs with neurorestorative properties are thought to be effective in both the acute and chronic phases of stroke. One significant example is Cerebrolysin, a combination of amino acids and peptides that mimic the biological functions of neurotrophic factors, which has been shown to improve outcomes after ischemic stroke, while preserving a promising safety profile. The purpose of this paper is to offer an overview on the role and impact of Cerebrolysin for ischemic stroke care, by touching on various aspects, from its complex, multimodal and pleiotropic mechanism of action, to its efficacy and safety, as well as cost effectiveness.
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Changes of Functional, Morphological, and Inflammatory Reactions in Spontaneous Peripheral Nerve Reinnervation after Thermal Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9927602. [PMID: 35154578 PMCID: PMC8826209 DOI: 10.1155/2022/9927602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/25/2021] [Accepted: 01/04/2022] [Indexed: 12/27/2022]
Abstract
In recent decades, the use of energy-based devices has substantially increased the incidence of iatrogenic thermal injury to nerves (cauterization, etc.). While recovery of the nerve after thermal injury is important, the changes in neural structure, function, and peripheral inflammatory reactions postinjury remain unclear. This study is aimed at demonstrating the changes mentioned above during the acute, subacute, and chronic stages of nerve reinnervation after thermal injury. Spontaneous reinnervation was evaluated, including the neural structures, nerve conduction abilities, and muscle regeneration. These effects vary depending on the severity of thermal injury (slight, moderate, and severe). Peripheral inflammatory reactions, as impediments to reinnervation, were found in significant numbers 3 days after thermal injury, exhibiting high expression of IL-1β and TNF-α, but low expression of IL-10. Our findings reveal the pathogenesis of peripheral nerve reinnervation after thermal injury, which will assist in selecting appropriate treatments in further research.
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Manousiouthakis E, Park J, Hardy JG, Lee JY, Schmidt CE. Towards the translation of electroconductive organic materials for regeneration of neural tissues. Acta Biomater 2022; 139:22-42. [PMID: 34339871 DOI: 10.1016/j.actbio.2021.07.065] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 07/23/2021] [Accepted: 07/27/2021] [Indexed: 12/13/2022]
Abstract
Carbon-based conductive and electroactive materials (e.g., derivatives of graphene, fullerenes, polypyrrole, polythiophene, polyaniline) have been studied since the 1970s for use in a broad range of applications. These materials have electrical properties comparable to those of commonly used metals, while providing other benefits such as flexibility in processing and modification with biologics (e.g., cells, biomolecules), to yield electroactive materials with biomimetic mechanical and chemical properties. In this review, we focus on the uses of these electroconductive materials in the context of the central and peripheral nervous system, specifically recent studies in the peripheral nerve, spinal cord, brain, eye, and ear. We also highlight in vivo studies and clinical trials, as well as a snapshot of emerging classes of electroconductive materials (e.g., biodegradable materials). We believe such specialized electrically conductive biomaterials will clinically impact the field of tissue regeneration in the foreseeable future. STATEMENT OF SIGNIFICANCE: This review addresses the use of conductive and electroactive materials for neural tissue regeneration, which is of significant interest to a broad readership, and of particular relevance to the growing community of scientists, engineers and clinicians in academia and industry who develop novel medical devices for tissue engineering and regenerative medicine. The review covers the materials that may be employed (primarily focusing on derivatives of fullerenes, graphene and conjugated polymers) and techniques used to analyze materials composed thereof, followed by sections on the application of these materials to nervous tissues (i.e., peripheral nerve, spinal cord, brain, optical, and auditory tissues) throughout the body.
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Affiliation(s)
- Eleana Manousiouthakis
- Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville 32611, FL, United States
| | - Junggeon Park
- School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea
| | - John G Hardy
- Department of Chemistry, Lancaster University, Lancaster LA1 4YB, United Kingdom; Materials Science Institute, Lancaster University, Lancaster LA1 4YB, United Kingdom.
| | - Jae Young Lee
- School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
| | - Christine E Schmidt
- Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville 32611, FL, United States.
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Stahnisch FW. A Century of Brain Regeneration Phenomena and Neuromorphological Research Advances, 1890s-1990s-Examining the Practical Implications of Theory Dynamics in Modern Biomedicine. Front Cell Dev Biol 2022; 9:787632. [PMID: 35071231 PMCID: PMC8773698 DOI: 10.3389/fcell.2021.787632] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/18/2021] [Indexed: 11/15/2022] Open
Abstract
The modern thesis regarding the "structural plastic" properties of the brain, as reactions to injuries, to tissue damage, and to degenerative cell apoptosis, can hardly be seen as expendable in clinical neurology and its allied disciplines (including internal medicine, psychiatry, neurosurgery, radiology, etc.). It extends for instance to wider research areas of clinical physiology and neuropsychology which almost one hundred years ago had been described as a critically important area for the brain sciences and psychology alike. Yet the mounting evidence concerning the range of structural neuroplastic phenomena beyond the significant early 3 years of childhood has shown that there is a progressive building up and refining of neural circuits in adaptation to the surrounding environment. This review essay explores the history behind multiple biological phenomena that were studied and became theoretically connected with the thesis of brain regeneration from Santiago Ramón y Cajal's pioneering work since the 1890s to the beginning of the American "Decade of the Brain" in the 1990s. It particularly analyzes the neuroanatomical perspectives on the adaptive capacities of the Central Nervous System (CNS) as well as model-like phenomena in the Peripheral Nervous System (PNS), which were seen as displaying major central regenerative processes. Structural plastic phenomena have assumed large implications for the burgeoning field of regenerative or restorative medicine, while they also pose significant epistemological challenges for related experimental and theoretical research endeavors. Hereafter, early historical research precursors are examined, which investigated brain regeneration phenomena in non-vertebrates at the beginning of the 20th century, such as in light microscopic studies and later in electron microscopic findings that substantiated the presence of structural neuroplastic phenomena in higher cortical substrates. Furthermore, Experimental physiological research in hippocampal in vivo models of regeneration further confirmed and corroborated clinical physiological views, according to which "structural plasticity" could be interpreted as a positive regenerative CNS response to brain damage and degeneration. Yet the underlying neuroanatomical mechanisms remained to be established and the respective pathway effects were only conveyed through the discovery of neural stem cells in in adult mammalian brains in the early 1990s. Experimental results have since emphasized the genuine existence of adult neurogenesis phenomena in the CNS. The focus in this essay will be laid here on questions of the structure and function of scientific concepts, the development of research schools among biomedical investigators, as well as the impact of new data and phenomena through innovative methodologies and laboratory instruments in the neuroscientific endeavors of the 20th century.
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Affiliation(s)
- Frank W. Stahnisch
- Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada
- Department of History, University of Calgary, Calgary, AB, Canada
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Kong LZ, Zhang RL, Hu SH, Lai JB. Military traumatic brain injury: a challenge straddling neurology and psychiatry. Mil Med Res 2022; 9:2. [PMID: 34991734 PMCID: PMC8740337 DOI: 10.1186/s40779-021-00363-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 12/27/2021] [Indexed: 12/12/2022] Open
Abstract
Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury (TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood-brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.
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Affiliation(s)
- Ling-Zhuo Kong
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Rui-Li Zhang
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Shao-Hua Hu
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. .,The Key Laboratory of Mental Disorder's Management in Zhejiang Province, Hangzhou, 310003, China. .,Brain Research Institute of Zhejiang University, Hangzhou, 310003, China. .,Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, 310003, China. .,MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University, Hangzhou, 310003, China.
| | - Jian-Bo Lai
- Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. .,The Key Laboratory of Mental Disorder's Management in Zhejiang Province, Hangzhou, 310003, China. .,Brain Research Institute of Zhejiang University, Hangzhou, 310003, China. .,Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, 310003, China. .,MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University, Hangzhou, 310003, China.
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Onose G, Anghelescu A, Blendea CD, Ciobanu V, Daia CO, Firan FC, Munteanu C, Oprea M, Spinu A, Popescu C. Non-invasive, non-pharmacological/bio-technological interventions towards neurorestoration upshot after ischemic stroke, in adults-systematic, synthetic, literature review. FRONT BIOSCI-LANDMRK 2021; 26:1204-1239. [PMID: 34856764 DOI: 10.52586/5020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/02/2021] [Accepted: 10/20/2021] [Indexed: 11/09/2022]
Abstract
Considering its marked life-threatening and (not seldom: severe and/or permanent) disabling, potential, plus the overall medico-psycho-socio-economic tough burden it represents for the affected persons, their families and the community, the cerebrovascular accident (CVA)-including with the, by far more frequent, ischemic type-is subject to considerable scientific research efforts that aim (if possible) at eliminating the stroke induced lesions, and consist, as well, in ambitious-but still poorly transferable into medical practice-goals such as brain neuroregeneration and/or repair, within related corollary/upshot of neurorestoration. We have conducted, in this respect, a systematic and synthetic literature review, following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" concept. Accordingly, we have interrogated five internationally renowned medical data bases: Elsevier, NCBI/PubMed, NCBI/PMC, PEDro, and ISI Web of Knowledge/Science (the last one to check whether the initially identified articles are published in ISI indexed journals), based on a large (details in the body text) number of most appropriate, to our knowledge, key word combinations/"syntaxes"-used contextually-and subsequently fulfilling the related, on five steps, filtering/selection methodology. We have thereby selected 114 fully eligible (of which contributive: 83-see further) papers; at the same time, additionally, we have enhanced our documentation-basically, but not exclusively, for the introductive part of this work (see further)-with bibliographic resources, overall connected to our subject, identified in the literature within a non-standardized search. It appears that the opportunity window for morph-functional recovery after stroke is larger than previously thought, actually being considered that brain neurorestoration/repair could occur, and therefore be expected, in later stages than in earlier ones, although, in this context, the number of cases possibly benefitting (for instance after physical and/or cognitive rehabilitation-including with magnetic or direct current transcranial stimulation) is quite small and with more or less conflicting, related outcomes, in the literature. Moreover, applying especially high intense, solicitating, rehabilitation interventions, in early stages post (including ischemic) stroke could even worsen the functional evolution. Accordingly, for clarifications and validation of more unitary points of view, continuing and boosting research efforts in this complex, interdisciplinary domain, is necessary. Until finding (if ever) effective modalities to cure the lesions of the central nervous system (CNS)-including post ischemic stroke-it is reasonable and recommendable-based on rigorous methodologies-the avail of combined ways: physiatric, pharmacologic, possibly also bio-technologic. On a different note, but however connected to our subject: periodic related systematic, synthetic literature reviews reappraisals are warranted and welcome.
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Affiliation(s)
- Gelu Onose
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Aurelian Anghelescu
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
- Specific Disciplines Department, Faculty of Midwifes and Nursing, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
| | - Corneliu Dan Blendea
- Medical-Surgical and Prophylactic Disciplines Department - Medical Rehabilitation, Recovery and Medical Physical Culture Discipline, Faculty of Medicine, University "Titu Maiorescu", 040051 Bucharest, Romania
- Physical and Rehabilitation Medicine & Balneology Clinic Division - The Neuro-Rehabilitation Compartment, Teaching Emergency Hospital of the Ilfov County, 22104 Bucharest, Romania
| | - Vlad Ciobanu
- Politehnica University of Bucharest, Computer Science Department, 060042 Bucharest, Romania
| | - Cristina Octaviana Daia
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Florentina Carmen Firan
- Physical and Rehabilitation Medicine & Balneology Clinic Division - The Neuro-Rehabilitation Compartment, Teaching Emergency Hospital of the Ilfov County, 22104 Bucharest, Romania
| | - Constantin Munteanu
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
- Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy "Grigore T. Popa" Iasi, 700454 Iasi, Romania
| | - Mihaela Oprea
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Aura Spinu
- Physical and Rehabilitation Medicine Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 020022 Bucharest, Romania
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
| | - Cristina Popescu
- Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania
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Huang Y, Wu W, Liu H, Chen Y, Li B, Gou Z, Li X, Gou M. 3D printing of functional nerve guide conduits. BURNS & TRAUMA 2021; 9:tkab011. [PMID: 34212061 PMCID: PMC8240533 DOI: 10.1093/burnst/tkab011] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Nerve guide conduits (NGCs), as alternatives to nerve autografts and allografts, have been widely explored as an advanced tool for the treatment of peripheral nerve injury. However, the repairing efficiency of NGCs still needs significant improvements. Functional NGCs that provide a more favorable microenvironment for promoting axonal elongation and myelination are of great importance. In recent years, 3D printing technologies have been widely applied in the fabrication of customized and complex constructs, exhibiting great potential for tissue engineering applications, especially for the construction of functional NGCs. In this review, we introduce the 3D printing technologies for manufacturing functional NGCs, including inkjet printing, extrusion printing, stereolithography-based printing and indirect printing. Further, we summarize the current methods and strategies for constructing functional NGCs, such as designing special conduit architectures, using appropriate materials and co-printing with different biological cues. Finally, the challenges and prospects for construction of functional NGCs are also presented.
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Affiliation(s)
- Yulan Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wenbi Wu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Haofan Liu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yuwen Chen
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Bo Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zhiyuan Gou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xun Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.,Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
| | - Maling Gou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
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