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Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

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Neural Regeneration Research 2025年第3期20卷 836-844页

作者： Do-Hun Lee Dan Cao Younghye Moon Chen Chen Nai-Kui Liu Xiao-Ming Xu Wei Wu spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA Department of Neuroscience Baylor College of MedicineHoustonTXUSA

spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

关键词： behavioral assessment motor function neural plasticity running wheel exercise spinal cord injury treadmill exercise voluntary exercise

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New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1699-1700页

作者： Seyed Mojtaba Hosseini Soheila Karimi-Abdolrezaee Department of Physiology and Pathophysiology Spinal Cord Research CentreRady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada Manitoba Multiple Sclerosis Research Center WinnipegMBCanada Children Hospital Research Institute of Manitoba WinnipegMBCanada

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

关键词： peroxidation Fischer injury

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Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie Lin Weihong Xu Department of spinal Surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and Research Center Peking University People’s HospitalBeijingChina Department of Orthopedic Surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

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Risk of prostate cancer in men with spinal cord n jury： a systematic review and meta-analysis

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Asian Journal of Andrology 2018年第6期20卷 555-560页

作者： Arcangelo Barbonetti Settimio D'ndrea Alessio Martorella Giorgio Felzani Sandro Francavilla Felice Francavilla spinal unit San Raffaele Sulmona InstituteSulmona 67039Italy Andrology unit Department of LifeHealth and Environmental SciencesUniversity of L＇AquilaL＇Aquila 67100Italy.

A lower risk of prostate cancer has been reported in men with spinal cord injury （SCI） as compared to that observed in able-bodied subjects. As injury-related consequences can have opposite effects on prostate pathophysiology, this meta-analysis aimed to （1） establish the existence/quantify the extent of decreased prostate cancer risk following SCI and （2） find out if there is any statistically significant difference in prostate-specific antigen （PSA） levels between SCI and able-bodied subjects. MEDLINE, Cochrane Library, Scopus, CINAHL, and ScienceDirect databases were used. Only studies reporting a prostate cancer diagnosis and/or PSA levels following SCI and in able-bodied controls were included. Five studies provided information about prostate cancer on 35 293 subjects with SCI and 158 140 controls. Six studies were included in PSA analysis which reported information on 391 men with SCI and 1921 controls. Pooled estimates indicated that SCI reduced the prostate cancer risk by approximately 50% as compared to controls, whereas differences in PSA levels were not statistically significant. Funnel plots suggested the presence of publication bias only in PSA analysis. Between-study heterogeneity was established and when, according to meta-regression models, analysis was restricted to studies including men with mean age over 55 years, prostate cancer risk in SCI decreased up to 65.0% than that in controls with no heterogeneity （P= 0.33, Iz = 9%）. In conclusion, in men over 55 years old, SCI decreases the prostate cancer risk up to 65.0% than that in controls. The large between-study heterogeneity on PSA confirms its poor reliability as a screening tool for prostate cancer in SCI.

关键词： paraplegia prostate cancer prostate-specific antigen quadriplegia spinal cord injury

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Repair mechanism of astrocytes and non-astrocytes in spinal cord injury

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World Journal of Clinical Cases 2020年第5期8卷 854-863页

作者： Xiang-Yun Liu Jian-Wei Guo Jian-Qiang Kou Yuan-Liang Sun Xiu-Jun Zheng Department of spinal Surgery The Affiliated Hospital of Qingdao University

BACKGROUND spinal cord injury(SCI)is a destructive disease that incurs huge personal and social costs,and there is no effective *** the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus,the pathogenesis of SCI is still under *** To determine the key genes based on the modularization of in-depth analysis,in order to identify the repair mechanism of astrocytes and non-astrocytes in *** Firstly,the differences between injured and non-injured spinal cord of astrocyte(HA),injured and non-injured spinal cord of non-astrocyte(FLOW),injured spinal cord of non-injured astrocyte(HA)and non-injured spinal cord of nonastrocyte(FLOW),and non-injured spinal cord of astrocyte(HA)and nonastrocyte(FLOW)were *** total number of differentially expressed genes was obtained by merging the four groups of differential ***,the genes were co-expressed and ***,the enrichment of GO function and KEGG pathway of module genes was ***,non-coding RNA,transcription factors and drugs that regulate module genes were predicted using hypergeometric *** In summary,we obtained 19 expression modules involving 5216 differentially expressed *** them,miR-494,XIST and other genes were differentially expressed in SCI patients,and played an active regulatory role in dysfunction module,and these genes were recognized as the driving genes of *** results showed that module genes were significantly involved in the biological processes of inflammation,oxidation and *** pathways such as NF-kappa B/A20,AMPK and MAPK were significantly *** addition,non-coding RNA pivot(including miR-136-5p and let-7d-5p,etc.)and transcription factor pivot(including NFKB1,MYC,etc.)were identified as significant regulatory dysfunction *** Overall,this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in

关键词： Astrocyte Non-astrocyte spinal cord injury Repair mechanism Dysfunction module Module genes

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Comparative proteomes change and possible role in different pathways of micro RNA-21a-5p in a mouse model of spinal cord injury

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Neural Regeneration Research 2020年第6期15卷 1102-1110页

作者： Almaghalsa-Ziad Mohammed Hong-Xia Du Hong-Liang Song Wei-Ming Gong Bin Ning Tang-Hong Jia Department of spinal Surgery Jinan Central Hospital Affiliated to Shandong University

Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly *** this study,a modified Allen's weight drop was used to establish a mouse model of spinal cord injury.A proteomics approach was used to understand the role of differential protein expression with miR-21 a-5 p knockdown,using a mouse model of spinal cord injury without gene knockout as a negative control *** found that after introducing miR-21 a-5 p knockdown,proteins that played an essential role in the regulation of inflammatory processes,cell protection against oxidative stress,cell redox homeostasis,and cell maintenance were upregulated compared with the negative control *** Encyclopedia of Genes and Genomes pathway enrichment analysis identified enriched pathways in both groups,such as the oxidative phosphorylation pathway,which is relevant to Parkinson's disease,Huntington's disease,Alzheimer's disease,and cardiac muscle *** also found that miR-21 a-5 p could be a potential biomarker for amyotrophic lateral sclerosis,as miR-21 a-5 p becomes deregulated in this *** results indicate successful detection of some important proteins that play potential roles in spinal cord *** the relationship between these proteins and the recovery of spinal cord injury will provide a reference for future research of spinal cord injury *** experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Shandong University of China on March 5,2014.

关键词： bioinformatics biomarker inflammation micro RNA mitochondria mouse pathway analysis proteomics spinal cord injury stathmin

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Autonomic dysreflexia: a cardiovascular disorder following spinal cord injury

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Neural Regeneration Research 2017年第9期12卷 1390-1400页

作者： Hisham Sharif Shaoping Hou spinal Cord Research Center Department of Neurobiology and Anatomy Drexel University College of Medicine

Autonomic dysreflexia （AD） is a serious cardiovascular disorder in patients with spinal cord injury （SCI）. The primary underlying cause of AD is loss of supraspinal control over sympathetic preganglionic neurons （SPNs） caudal to the injury, which renders the SPNs hyper-responsive to stimulation. Central maladaptive plasticity, including C-fiber sprouting and propriospinal fiber proliferation exaggerates noxious afferent transmission to the SPNs, causing them to release massive sympathetic discharges that result in severe hypertensive episodes. In parallel, upregulated peripheral vascular sensitivity following SCI exacerbates the hypertensive response by augmenting gastric and pelvic vasoconstriction. Currently, the majority of clinically employed treatments for AD involve anti-hypertensive medications and Botox injections to the bladder. Although these approaches mitigate the severity of AD, they only yield transient effects and target the effector organs, rather than addressing the primary issue of central sympathetic dysregulation. As such, strategies that aim to restore supraspinal reinnervation of SPNs to improve cardiovascular sympathetic regulation are likely more effective for AD. Recent pre-clinical investigations show that cell transplantation therapy is efficacious in reestablishing spinal sympathetic connections and improving hemodynamic per- formance, which holds promise as a potential therapeutic approach.

关键词： autonomic dysreflexia hyper-reflexia sympathetic dysfunction C-fibers propriospinal axons a-adrenoceptors stem cell transplantation

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Role of chondroitin sulfate proteoglycan signaling in regulating neuroinflammation following spinal cord injury

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Neural Regeneration Research 2018年第12期13卷 2080-2082页

作者： Scott M.Dyck Soheila Karimi-Abdolrezaee Department of Physiology and Pathophysiology the Regenerative Medicine Program the Spinal Cord Research Center University of Manitoba

spinal cord injury （SCI） elicits a robust inflammatory response that is a hallmark of the secondary injury mechanisms. Neuroinflammation is orchestrated initially by the response of resident astrocytes and microglia to injury, which subsequently facilitates the recruitment of peripheral immune cells into the SCI lesion （Orr and Gensel, 2018）. This inflammatory response contributes to cell death and tissue degeneration through the production of pro-inflammatory cytokines and chemokines, free radicals and proteolytic enzymes. However, neuroinflammatory cells also play beneficial regulatory role in repair mechanisms after SCI by adopting a reparative and wound healing phenotype （Orr and Gensel, 2018; Tran et al., 2018）. Hence, understanding the underlying mechanisms by which immune cells are reg- ulated within the microenvironment of injury would aid in harnessing the reparative potential of inflammation following SCI.

关键词： Role of chondroitin sulfate proteoglycan signaling in regulating neuroinflammation following spinal cord injury PTP SCI

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Reduced non-CpG methylation is a potential epigenetic target after spinal cord injury

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Neural Regeneration Research 2023年第11期18卷 2489-2496页

作者： Zhourui Wu Chen Li Ran Zhu Yiqiu Cao Thomas C.Chen Liming Cheng Key Laboratory of Spine and spinal cord Injury Repair and Regeneration(Tongji University) Ministry of EducationShanghaiChina Division of Spine Department of OrthopedicsTongji HospitalTongji University School of MedicineShanghaiChina Institute of spinal and spinal Cord Injury Tongji University School of MedicineShanghaiChina Department of Neurosurgery Keck School of MedicalUniversity of Southern CaliforniaLos AngelesCAUSA

DNA methylation is a critical epigenetic regulator in the occurrence and development of diseases and is closely related to various functional responses in relation to spinal cord *** investigate the role of DNA methylation in spinal cord injury,we constructed a library with reduced-representation bisulfite sequencing data obtained at various time points(day 0-42)after spinal cord injury in *** DNA methylation levels,specifically non-CpG(CHG and CHH)methylation levels,decreased modestly following spinal cord *** post-spinal cord injury were classified as early(day 0-3),intermediate(day7-14),and late(day 28-42)based on similarity and hie rarchical cluste ring of global DNA methylation *** non-CpG methylation level,which included CHG and CHH methylation levels,was markedly reduced despite accounting for a minor proportion of total methylation *** multiple genomic sites,including the 5’untranslated regions,promoter,exon,intron,and 3’untranslated regions,the non-CpG methylation level was markedly decreased following spinal cord injury,whereas the CpG methylation level remained unchanged at these *** one-half of the differentially methylated regions were located in intergenic areas;the other differentially methylated regions in both CpG and non-CpG regions were cluste red in intron regions,where the DNA methylation level was *** function of genes associated with differentially methylated regions in promoter regions was also *** Gene Ontology analysis results,DNA methylation was implicated in a number of essential functional responses to spinal cord injury,including neuronal synaptic connection creation and axon ***,neither CpG methylation nor non-CpG methylation was implicated in the functional response of glial or inflammatory *** summary,our work elucidated the dynamic pattern of DNA methylation in the spinal co rd following injury and identified reduced nonCpG meth

关键词： CpG methylation cytosine fraction differentially methylated regions DNA methylation DNA methyltransferases dynamic signatures Gene Ontology non-CpG methylation single-cell RNA-Seq spinal cord injury

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