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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 被引量:2
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作者 Sumei Liu Baoguo Liu +4 位作者 Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期440-446,共7页
Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a... Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced 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 model.Basso,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 core.Examination 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 microenvironment.Altogether,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 site.Graft-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. 展开更多
关键词 biomaterial FIBRINOGEN functional recovery induced neural stem cell transplantation MICROENVIRONMENT MICROGLIA spinal cord injury THROMBIN
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Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury 被引量:1
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作者 Jiang Cao Xiao Yu +10 位作者 Jingcheng Liu Jiaju Fu Binyu Wang Chaoqin Wu Sheng Zhang Hongtao Chen Zi Wang Yinyang Xu Tao Sui Jie Chang Xiaojian Cao 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第11期2499-2512,共14页
The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arth... The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury. 展开更多
关键词 astrocytes EAAT2 EXCITOTOXICITY glutamate homeostasis JAK-STAT pathway locomotor function NEUROTOXICITY RUXOLITINIB spinal cord injury transcriptome analysis
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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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作者 Wenrui Qu Xiangbing Wu +13 位作者 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 《Neural Regeneration Research》 SCIE CAS 2025年第5期1467-1482,共16页
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... 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 cord.Here 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 injury.We 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 directions.Such 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 functions.Importantly,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 injury.These 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. 展开更多
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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Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis
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作者 Sihong Huang Jungong Han +4 位作者 Hairong Zheng Mengjun Li Chuxin Huang Xiaoyan Kui Jun Liu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第7期1553-1558,共6页
Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely u... Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly understood.Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain injury.This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function.However,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional connectivity.Given that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is critical.In the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury.In this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy controls.Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis.In the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network.More than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 patients.Furthermore,better cognitive function was associated with more efficient networks.Finally,our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury.These findings highlight the importance of integrating structural and functional connectivity in unde rstanding the occurrence and evolution of mild traumatic brain injury.Additionally,exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury. 展开更多
关键词 cognitive function CROSS-SECTION FOLLOW-UP functional connectivity graph theory longitudinal study mild traumatic brain injury prediction small-worldness structural connectivity subnetworks whole brain network
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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats
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作者 Yunting Xiang Xiangxin Xing +6 位作者 Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu 《Neural Regeneration Research》 SCIE CAS 2025年第5期1495-1504,共10页
Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network lev... Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery. 展开更多
关键词 brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity
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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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作者 Do-Hun Lee Dan Cao +4 位作者 Younghye Moon Chen Chen Nai-Kui Liu Xiao-Ming Xu Wei Wu 《Neural Regeneration Research》 SCIE CAS 2025年第3期836-844,共9页
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 ... 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. 展开更多
关键词 behavioral assessment motor function neural plasticity running wheel exercise spinal cord injury treadmill exercise voluntary exercise
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Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation
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作者 Yafan Bai Hui Ma +5 位作者 Yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li 《Neural Regeneration Research》 SCIE CAS 2025年第8期2325-2336,共12页
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0... Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury. 展开更多
关键词 antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury
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Effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries
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作者 Zhi-Ying Chen Meng-Hua Wang Zhong Ye 《World Journal of Clinical Cases》 SCIE 2024年第21期4582-4589,共8页
BACKGROUND The rotator cuff is located below the acromion and deltoid muscles and comprises multiple tendons that wrap around the humeral head,maintaining shoulder joint stability.AIM To explore the effect of electroa... BACKGROUND The rotator cuff is located below the acromion and deltoid muscles and comprises multiple tendons that wrap around the humeral head,maintaining shoulder joint stability.AIM To explore the effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries.METHODS We selected 97 patients with rotator cuff injuries treated in the People's Hospital of Yuhuan from February 2020 to May 2023.Patients were grouped using the envelope method.RESULTS After treatment,the study group’s treatment effective rate was 94.90%(46/49 patients),significantly higher than that in the control group(79.17%,38/48 cases;P<0.05).Before treatment,there was no difference in Constant Murley Score(CMS)scores,shoulder mobility,or 36-Item Short Form Health Survey(SF-36)scale scores(P>0.05).Compared with those before treatment,the CMS scores(including pain,daily living ability,shoulder mobility,and muscle strength),all aspects of shoulder mobility(forward flexion,posterior extension,external rotation,internal rotation),and SF-36 scale scores(including physiological,psychological,emotional,physical,vitality,and health status)were higher in both groups after treatment and significantly higher in the study group(P<0.05).There was no difference in the occurrence of complications between the two treatment groups(P>0.05).CONCLUSION Electroacupuncture combined with rehabilitation techniques has a good treatment effect on patients with rotator cuff injuries,helps accelerate the recovery of shoulder function,improves the quality of life,and is highly safe. 展开更多
关键词 Electroacupuncture therapy Rehabilitation technique Rotator cuff injury Shoulder joint function
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Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex
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作者 Yan Li Peng Hao +6 位作者 Hongmei Duan Fei Hao Wen Zhao Yudan Gao Zhaoyang Yang Kwok-Fai So Xiaoguang Li 《Neural Regeneration Research》 SCIE CAS 2025年第10期2923-2937,共15页
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne... The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries. 展开更多
关键词 adult endogenous neurogenesis basic fibroblast growth factor-hyaluronic acid collagen gel cortical remodeling functional recovery migration motor cortex injury neural circuits neural stem cells newborn neurons proliferation
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Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury:a resting-state functional MRI study 被引量:1
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作者 Cheng-Cheng Sun Yu-Wen Zhang +10 位作者 Xiang-Xin Xing Qi Yang Ling-Yun Cao Yu-Feng Cheng Jing-Wang Zhao Shao-Ting Zhou Dan-Dan Cheng Ye Zhang Xu-Yun Hua He Wang Dong-Sheng Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第2期410-415,共6页
Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctua... Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury. 展开更多
关键词 amplitude of low frequency fluctuation cortical plasticity functional magnetic resonance imaging modified constraint-induced movement therapy traumatic brain injury
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A new peptide,VD11,promotes structural and functional recovery after spinal cord injury
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作者 Shan-Shan Li Bai-Yu Zhang +11 位作者 Sai-Ge Yin Zi-Qi Wei Nai-Xin Liu Yi-Lin Li Si-Yu Wang Yu-Heng Shi Jian Zhao Li-Juan Wang Yue Zhang Jun Sun Ying Wang Xin-Wang Yang 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第10期2260-2267,共8页
The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote stru... The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury.Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue.While amphibians have a pronounced ability to regenerate the spinal cord,few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury.Here we report for the first time the successful identification and isolation of a new polypeptide,VD11(amino acid sequence:VDELWPPWLPC),from the spinal cord of an endemic Chinese amphibian(Odorrana schmackeri).In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide,as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia.In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury,alleviated pathological damage,and promoted axonal regeneration.Furthermore,RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways.In summary,we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury. 展开更多
关键词 Akt signaling pathway amphibian-derived bioactive peptide AMPK signaling pathway axonal regeneration brain-derived neurotrophic factor ischemia/reperfusion injury motor function nerve growth factor neuroprotective effect spinal cord injury
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Ex vivo non-viral vector-mediated neurotrophin-3 gene transfer to olfactory ensheathing glia: effects on axonal regeneration and functional recovery after implantation in rats with spinal cord injury 被引量:3
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作者 吴军 孙天胜 +1 位作者 任继鑫 王献章 《Neuroscience Bulletin》 SCIE CAS CSCD 2008年第2期57-65,共9页
Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI... Objective Combine olfactory ensheathing glia (OEG) implantation with ex vivo non-viral vector-based neurotrophin- 3 (NT-3) gene therapy in attempting to enhance regeneration after thoracic spinal cord injury (SCI). Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 (+)-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord (T9) contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 (+)-NT3 or pcDNA3.1 (+) plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 (+)-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats. 展开更多
关键词 functional recovery gene therapy NEUROTROPHIN-3 olfactory ensheathing glia regeneration spinal cord injury non-viral vectors
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A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats 被引量:4
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作者 Jie Yang Chia-Chen Hsu +3 位作者 Ting-Ting Cao Hua Ye Jing Chen Yun-Qing Li 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第3期657-663,共7页
A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regen... A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects. 展开更多
关键词 functional recovery granular hydrogel hyaluronic acid myelin sheath nerve conduit nerve regeneration peripheral nerve regeneration sciatic nerve injury tissue engineering transection injury
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Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury 被引量:6
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作者 Yu Kang Rui Zhu +4 位作者 Shuang Li Kun-Peng Qin Hao Tang Wen-Shan Shan Zong-Sheng Yin 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第4期881-888,共8页
Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotectiv... Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury. 展开更多
关键词 ERYTHROPOIETIN ferroptosis Gpx4 iron overload lipid peroxidation mechanism neurological function recovery spinal cord injury spinal neuron xCT
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Double-target neural circuit-magnetic stimulation improves motor function in spinal cord injury by attenuating astrocyte activation 被引量:6
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作者 Dan Zhao Ye Zhang +5 位作者 Ya Zheng Xu-Tong Li Cheng-Cheng Sun Qi Yang Qing Xie Dong-Sheng Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第5期1062-1066,共5页
Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In... Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1β, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury. 展开更多
关键词 ASTROCYTE inflammatory response microtubule-associated protein 2 motor function motor-evoked potential neural circuit-magnetic stimulation neural repair neuromodulation technique spinal cord injury synaptic plasticity
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The pig as a preclinical traumatic brain injury model:current models,functional outcome measures,and translational detection strategies 被引量:8
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作者 Holly A.Kinder Emily W.Baker Franklin D.West 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第3期413-424,共12页
Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the... Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions. 展开更多
关键词 traumatic brain injury large animal MODEL PIG MODEL diffuse AXONAL injury functional outcome assessment measures controlled cortical impact MODEL fluid percussion injury MODEL magnetic resonance imaging biomarkers
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Small-worldness of brain networks after brachial plexus injury: a resting-state functional magnetic resonance imaging study 被引量:6
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作者 Wei-Wei Wang Ye-Chen Lu +4 位作者 Wei-Jun Tang Jun-Hai Zhang Hua-Ping Sun Xiao-Yuan Feng Han-Qiu Liu 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第6期1061-1065,共5页
Research on brain function after brachial plexus injury focuses on local cortical functional reorganization,and few studies have focused on brain networks after brachial plexus injury.Changes in brain networks may hel... Research on brain function after brachial plexus injury focuses on local cortical functional reorganization,and few studies have focused on brain networks after brachial plexus injury.Changes in brain networks may help understanding of brain plasticity at the global level.We hypothesized that topology of the global cerebral resting-state functional network changes after unilateral brachial plexus injury.Thus,in this cross-sectional study,we recruited eight male patients with unilateral brachial plexus injury(right handedness,mean age of 27.9±5.4years old)and eight male healthy controls(right handedness,mean age of 28.6±3.2).After acquiring and preprocessing resting-state magnetic resonance imaging data,the cerebrum was divided into 90 regions and Pearson’s correlation coefficient calculated between regions.These correlation matrices were then converted into a binary matrix with affixed sparsity values of 0.1–0.46.Under sparsity conditions,both groups satisfied this small-world property.The clustering coefficient was markedly lower,while average shortest path remarkably higher in patients compared with healthy controls.These findings confirm that cerebral functional networks in patients still show smallworld characteristics,which are highly effective in information transmission in the brain,as well as normal controls.Alternatively,varied small-worldness suggests that capacity of information transmission and integration in different brain regions in brachial plexus injury patients is damaged. 展开更多
关键词 nerve regeneration brachial plexus injury functional magnetic resonance imaging small-world network small-world property topology properties functional reorganization clustering coefficient shortest path peripheral nerve injury neural regeneration
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Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia 被引量:8
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作者 Dong Wang Jianjun Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第10期749-755,共7页
Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein whi... Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours (mild hypothermia). Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells (bromodeoxyuridine-positive cells), better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury. 展开更多
关键词 bone marrow mesenchymal stem cells electrophysiological function HYPOTHERMIA spinal cord hemisection injury TRANSPLANTATION
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Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury 被引量:9
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作者 Aysegul Gunduz John Rothwell +1 位作者 Joan Vidal Hatice Kumru 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第12期1933-1938,共6页
We conducted a systematic review of studies using non-invasive brain stimulation(NIBS: repetitive transcranial magnetic stimulation(r TMS) and transcranial direct current stimulation(t DCS)) as a research and c... We conducted a systematic review of studies using non-invasive brain stimulation(NIBS: repetitive transcranial magnetic stimulation(r TMS) and transcranial direct current stimulation(t DCS)) as a research and clinical tool aimed at improving motor and functional recovery or spasticity in patients following spinal cord injury(SCI) under the assumption that if the residual corticospinal circuits could be stimulated appropriately, the changes might be accompanied by functional recovery or an improvement in spasticity. This review summarizes the literature on the changes induced by NIBS in the motor and functional recovery and spasticity control of the upper and lower extremities following SCI. 展开更多
关键词 spinal cord injury non-invasive brain stimulation transcranial magnetic stimulation transcranialdirect current stimulation functional improvement SPASTICITY neuropathic pain
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Gait and Glasgow Coma Scale scores can predict functional recovery in patients with traumatic brain injury 被引量:3
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作者 Sevil Bilgin Arzu Guclu-Gunduz +2 位作者 Hakan Oruckaptan Nezire Kose Bülent Celik 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第25期1978-1984,共7页
Fifty-one patients with mild (n -- 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score Functional le... Fifty-one patients with mild (n -- 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury. 展开更多
关键词 brain injury traumatic brain injury REHABILITATION early rehabilitation function PROGNOSIS GlasgowComa Scale Glasgow Outcome ScaLe functional level neural regeneration
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