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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration Research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen Cell Therapy Center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina Center of Neural injury and Repair Beijing Institute for Brain DisordersBeijingChina Center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury ***,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion *** of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the ***,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion ***-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

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Continued development of azithromycin as a neuroprotective therapeutic for the treatment of spinal cord injury and other neurological conditions

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Neural Regeneration Research 2021年第3期16卷 508-509页

作者： Timothy J.Kopper John C.Gensel spinal cord and Brain injury Research Center Department of PhysiologyUniversity of KentuckyLexingtonKYUSA

spinal cord injury(SCI)induces a robust inflammatory response largely mediated by resident microglia and infiltrating macrophages across the blood-brain *** these cell populations are capable of promoting repair and regenerative responses,in the days and weeks after SCI they predominately adopt pro-inflammatory profiles known to inhibit recovery and potentiate secondary injury pathways.

关键词： protective injury therapeutic

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Low-dose testosterone replacement therapy and electrically evoked resistance training enhance muscle quality after spinal cord injury

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Neural Regeneration Research 2021年第8期16卷 1544-1545页

作者： Raymond E.Lai Ashraf S.Gorgey spinal cord injury and disorders Hunter Holmes McGuire VA Medical CenterPhysical Medicine and RehabilitationVirginia Commonwealth UniversityRichmondVIUSA

The current perspective is aimed to highlight the significance of adding low-dose testosterone replacement therapy(TRT) to electrically evoked resistance training(RT).Evoked RT is primarily designed to load the paralyzed lower extremity muscles to elicit muscle hypertrophy in persons with spinal cord injury(SCI)(Ryan et al.,2013;Gorgey et al.,2019).The rationale was based on previous work that indicated that highdose TRT is likely to enhance muscle quality。

关键词： TRT rational likely

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Kdm6a-CNN1 axis orchestrates epigenetic control of traumainduced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair

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Bone Research 2024年第2期12卷 314-333页

作者： Chengjun Li Tian Qin Jinyun Zhao Yuxin Jin Yiming Qin Rundong He Tianding Wu Chunyue Duan Liyuan Jiang Feifei Yuan Hongbin Lu Yong Cao Jianzhong Hu Department of Sports Medicine Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China Key Laboratory of Organ injury Aging and Regenerative Medicine of Hunan ProvinceXiangya Road 87Changsha 410008China National Clinical Research Center for Geriatric disorders Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China Department of Spine Surgery and Orthopaedics Xiangya HospitalCentral South UniversityXiangya Road 87Changsha 410008China

Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory *** extensive investigations into vascular senescence associated with aging and degenerative diseases,the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress,particularly its involvement in senescence-induced inflammation,remain insufficiently *** this study,we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury(SCI).Lysine demethylase 6A(Kdm6a),commonly known as UTX,emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells(SCMECs).Upregulation of UTX induces senescence in SCMECs,leading to an amplified release of proinflammatory factors,specifically the senescenceassociated secretory phenotype(SASP)components,thereby modulating the inflammatory ***,the deletion of UTX in endothelial cells shields SCMECs against senescence,mitigates the release of proinflammatory SASP factors,and promotes neurological functional recovery after *** forms an epigenetic regulatory axis by binding to calponin 1(CNN1),orchestrating trauma-induced SCMECs senescence and SASP secretion,thereby influencing neuroinflammation and neurological functional ***,local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion,reinstating a local regenerative microenvironment and enhancing functional repair after *** conclusion,targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion,alleviate neuroinflammation,and provide a novel treatment strategy for SCI repair.

关键词： inflammation epigenetic neurological

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Skeletal muscle conditioning may be an effective rehabilitation intervention preceding functional electrical stimulation cycling

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Neural Regeneration Research 2016年第8期11卷 1232-1233页

作者： Rodney C.Wade Ashraf S.Gorgey spinal cord injury and disorders Service Hunter Holmes McGuire Department of Veterans Affairs Medical Center Department of Physical Medicine and Rehabilitation Virginia Commonwealth University

In our recent effort,we introduced a submaximal index that utilized ventilatory efficiency relative to CO2 production（VE/CO2）to evaluate the cardiovascular effectiveness to functional electrical stimulation lower-ex... 详细信息

关键词： cycling stimulation conditioning rehabilitation resting cardiovascular utilized extremity intramuscular prior

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Robotic exoskeletons: The current pros and cons

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World Journal of Orthopedics 2018年第9期9卷 112-119页

作者： Ashraf S Gorgey spinal cord injury and disorders Center Hunter Holmes McGuire VAMC Department of Physical Medicine and Rehabilitation Virginia Commonwealth University

Robotic exoskeletons have emerged as rehabilitation tool that may ameliorate several of the existing healthrelated consequences after spinal cord injury(SCI).However,evidence to support its clinical application is still lacking considering their prohibitive *** current mini-review is written to highlight the main limitations and potential benefits of using exoskeletons in the rehabilitation of persons with *** have recognized two main areas relevant to the design of exoskeletons and to their applications on major health consequences after *** design prospective refers to safety concerns,fitting time and speed of *** health prospective refers to factors similar to body weight,physical activity,pressure injuries and bone *** trials are currently underway to address some of these limitations and to maximize the benefits in rehabilitation *** directions highlight the need to use exoskeletons in conjunction with other existing and emerging technologies similar to functional electrical stimulation and brain-computer interface to address major *** have the potential to revolutionize rehabilitation following SCI;however,it is still premature to make solid recommendations about their clinical use after SCI.

关键词： spinal cord injury Exoskeleton Robotics Rehabilitation Locomotion

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Semi-automated segmentation of magnetic resonance images for thigh skeletal muscle and fat using threshold technique after spinal cord injury

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Neural Regeneration Research 2018年第10期13卷 1787-1795页

作者： Mina P.Ghatas Robert M.Lester M.Rehan Khan Ashraf S.Gorgey Department of spinal cord injury and disorders Hunter Holmes McGuire VA Medical Center Department of Radiology Hunter Holmes McGuire VA Medical Center Department of Physical Medicine and Rehabilitation Virginia Commonwealth University

Magnetic resonance imaging is considered the ＂gold standard＂ technique for quantifying thigh muscle and fat cross-sectional area. We have developed a semi-automated technique to segment seven thigh compartments in persons with spinal cord injury. Thigh magnetic resonance images from 18 men（18–50 years old） with traumatic motor-complete spinal cord injury were analyzed in a blinded fashion using the threshold technique. The cross-sectional area values acquired by thresholding were compared to the manual tracing technique. The percentage errors for thigh circumference were（threshold： 170.71 ± 38.67; manual： 169.45 ± 38.27 cm2） 0.74%, subcutaneous adipose tissue（threshold： 65.99±30.79; manual： 62.68 ± 30.22） 5.2%, whole muscle（threshold： 98.18 ± 20.19; manual： 98.20 ± 20.08 cm2） 0.13%, femoral bone（threshold： 6.53 ± 1.09; manual： 6.53 ± 1.09 cm2） 0.64%, bone marrow fat（threshold： 3.12 ± 1.12; manual： 3.1 ± 1.11 cm2） 0.36%, knee extensor（threshold： 43.98 ± 7.66; manual： 44.61 ± 7.81 cm2） 1.78% and % intramuscular fat（threshold： 10.45 ± 4.29; manual： 10.92 ± 8.35%） 0.47%. Collectively, these results suggest that the threshold technique provided a robust accuracy in measuring the seven main thigh compartments, while greatly reducing the analysis time.

关键词： spinal cord injury magnetic resonance imaging semi-automated segmentation subcutaneous adipose tissue intramuscular fat

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Potential physiological and pathological roles for axonal ryanodine receptors

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Neural Regeneration Research 2023年第4期18卷 756-759页

作者： David P.Stirling Kentucky spinal cord injury Research Center and Departments of Neurological Surgery Anatomical Sciences and NeurobiologyMicrobiology and ImmunologyUniversity of LouisvilleSchool of MedicineLouisvilleKYUSA

Clinical disability following trauma or disease to the spinal cord often involves the loss of vital white matter elements including axons and *** excessive Cais an established driver of axonal degeneration,therapeutically targeting externally sourced Cato date has had limited success in both basic and clinical *** factors that may underlie this limited success include the complexity of the many potential sources of Caentry and the discovery that axons also contain substantial amounts of stored Cathat if inappropriately released could contribute to axonal *** Castorage is largely accomplished by the axoplasmic reticulum that is part of a continuous network of the endoplasmic reticulum that provides a major sink and source of intracellular Cafrom the tips of dendrites to axonal ***“neuron-within-a-neuron”is positioned to rapidly respond to diverse external and internal stimuli by amplifying cytosolic Calevels and generating short and long distance regenerative Cawaves through Cainduced *** review provides a glimpse into the molecular machinery that has been implicated in regulating ryanodine receptor mediated Carelease in axons and how dysregulation and/or overstimulation of these internodal axonal signaling nanocomplexes may directly contribute to Ca-dependent axonal *** ryanodine receptors expressed in dendrites,soma,and axonal terminals have been implicated in synaptic transmission and synaptic plasticity,but a physiological role for internodal localized ryanodine receptors remains largely *** physiological roles for internodal ryanodine receptors and such an elaborate internodal binary membrane signaling network in axons will also be discussed.

关键词： axomyelinic synapse axon axoplasmic reticulum calcium ryanodine receptor secondary axonal degeneration spinal cord injury voltage-gated calcium channel white matter injury

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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Skeletal muscle mitochondrial health and spinal cord injury

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世界骨科杂志：英文版 2016年第10期7卷 628-637页

作者： Laura C O'Brien Ashraf S Gorgey spinal cord injury and disorders Service Hunter Holmes McGuire VA Medical Center Department of Physiology and Biophysics Virginia Commonwealth University Department of Physical Medicine and Rehabilitation Virginia Commonwealth University

Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury(SCI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type Ⅱ diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic SCI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with SCI to type Ⅱ diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following SCI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic SCI.

关键词： Mitochondria spinal cord injuries Body composition Diabetes mellitus Obesity Metabolism

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