Our previo us study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes(hNSC-Exo)in ischemic stroke.Here,we loaded brain-derived neurotrophic factor(BDNF)into exosomes derived from N...Our previo us study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes(hNSC-Exo)in ischemic stroke.Here,we loaded brain-derived neurotrophic factor(BDNF)into exosomes derived from NSCs to construct engineered exosomes(BDNF-hNSC-Exo)and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo.In a model of H_(2)O_(2)-induced oxidative stress in NSCs,BDNF-hNSC-Exo markedly enhanced cell survival.In a rat middle cerebral arte ry occlusion model,BDNF-hNSC-Exo not only inhibited the activation of microglia,but also promoted the differentiation of endogenous NSCs into neurons.These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stro ke.Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.展开更多
Current management for spinal cord injury aims to reduce secondary damage and recover sensation and movement.Acute spinal cord injury is often accompanied by spinal cord compartment syndrome.Decompression by durotomy ...Current management for spinal cord injury aims to reduce secondary damage and recover sensation and movement.Acute spinal cord injury is often accompanied by spinal cord compartment syndrome.Decompression by durotomy and/or myelotomy attempts to relieve secondary damage by completelyrelieving the compression of the spinal cord,removing the necrotic tissue,decreasing edema,reducing hemorrhage,and improving blood circulation in the spinal cord.However,it is controversial whether durotomy and/or myelotomy after spinal cord injury are beneficial to neurological recovery.This review compares the clinical effects of durotomy with those of myelotomy in the treatment of spinal cord injury.We found that durotomy has been performed more than myelotomy in the clinic,and that durotomy may be safer and more effective than myelotomy.Durotomy performed in humans had positive effects on neurological function in 92.3% of studies in this review,while durotomy in animals had positive effects on neurological function in 83.3% of studies.Myelotomy procedures were effective in 80% of animal studies,but only one clinical study of myelotomy has reported positive results,of motor and sensory improvement,in humans.However,a number of new animal studies have reported that durotomy and myelotomy are ineffective for spinal cord injury.More clinical data,in the form of a randomized controlled study,are needed to understand the effectiveness of durotomy and myelotomy.展开更多
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
Stroke is a main cause of death and disability worldwide.The ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that...Stroke is a main cause of death and disability worldwide.The ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that may give substantial and possibly complete recovery of brain function after stroke.Many animal models and clinical trials have demonstrated that neural stem cells(NSCs)in the central nervous system can orchestrate neurological repair through nerve regeneration,neuron polarization,axon pruning,neurite outgrowth,repair of myelin,and remodeling of the microenvironment and brain networks.Compared with other types of stem cells,NSCs have unique advantages in cell replacement,paracrine action,inflammatory regulation and neuroprotection.Our review summarizes NSC origins,characteristics,therapeutic mechanisms and repair processes,then highlights current research findings and clinical evidence for NSC therapy.These results may be helpful to inform the direction of future stroke research and to guide clinical decision-making.展开更多
Stroke remains the leading cause of long-term disability.Hemiparesis is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor co...Stroke remains the leading cause of long-term disability.Hemiparesis is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor cortex.As the only direct descending motor pathway,the corticospinal tract(CST)is the primary pathway to innervate spinal motor neurons,and thus,forms the neuroanatomical basis to control the peripheral muscles for voluntary movements.Here,we review evidence from both experimental animals and stroke patients,regarding CST axonal damage,functional contribution of CST axonal integrity and remodeling to neurological recovery,and therapeutic approaches aimed to enhance CST axonal remodeling after stroke.The new insights gleaned from preclinical and clinical studies may encourage the development of more rational therapeutics with a strategy targeted to promote axonal rewiring for corticospinal innervation,which will significantly impact the current clinical needs of subacute and chronic stroke treatment.展开更多
Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promo...Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.展开更多
Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as th...Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as the main search terms,all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed,EMBASE,MEDLINE,Web of Science,Science Direct,China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases by computer.The search was conducted from their inception date to April 2017.No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations.Two reviewers independently selected studies according to the title,abstract and full text.The risk of bias in the included studies was also evaluated.Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso,Beattie,and Bresnahan scale score,inclined plane score and Gale’s motor function score.Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels,malondialdehyde levels,nitric oxide synthase activity,nitric oxide levels,xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor.The results of meta-analysis showed that compared with the control group,resveratrol significantly increased the Basso,Beattie,and Bresnahan scale scores after spinal cord injury(n=300,mean difference(MD)=3.85,95%confidence interval(CI)[2.10,5.59],P<0.0001).Compared with the control group,superoxide dismutase levels were significantly elevated(n=138,standardized mean difference(SMD)=5.22,95%CI[2.98,7.45],P<0.00001),but malondialdehyde levels were significantly diminished(n=84,SMD=–3.64,95%CI[–5.84,–1.43],P=0.001)in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurologi展开更多
Leukemia inhibitory factor(LIF) contributes to the neuroprotection by neural stem cells(NSCs) after ischemic stroke. Our aim was to explore whether LIFtransfected NSCs(LIF-NSCs) can ameliorate brain injury and promote...Leukemia inhibitory factor(LIF) contributes to the neuroprotection by neural stem cells(NSCs) after ischemic stroke. Our aim was to explore whether LIFtransfected NSCs(LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro.Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion(MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injuryin the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.展开更多
Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits.In previous epidural electrical stimulation studies,single electrode sites and con...Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits.In previous epidural electrical stimulation studies,single electrode sites and continuous tetanic stimulation have often been used.With this stimulation,the body is prone to declines in tolerance and locomotion coordination.In the present study,rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers,and were then subjected to epidural electrical stimulation.The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment.Simultaneously,the electrode stimulation site was able to be accurately applied to the L2–3 and S1 segments of the spinal cord.To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes,GFAP/Iba-1 doublelabeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation.Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation,and there was no activated Iba-1~+cell aggregation,indicating that the implant did not cause an inflammatory response in the spinal cord.Rat gait analysis showed that,at 3 days after surgery,gait became coordinated in rats with spinal cord injury under burst stimulation.The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution.To evaluate the matching degree between the flexible epidural electrode(including three stimulation contacts),vertebral morphology,and the level of the epidural site of the stimulation electrode,micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation.Based on the experimental results of gait recover展开更多
For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein th...For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.展开更多
The evaluation of such novel therapies for acute spinal cord injury in clinical trials is extremely challenging.Our current dependence upon the clinical assessment of neurologic impairment renders many acute SCI patie...The evaluation of such novel therapies for acute spinal cord injury in clinical trials is extremely challenging.Our current dependence upon the clinical assessment of neurologic impairment renders many acute SCI patients ineligible for trials because they are not examinable.Furthermore,the difficulty in predicting neurologic recovery based on the early clinical assessment forces investigators to recruit large cohorts to have sufficient power.Biomarkers that objectively classify injury severity and better predict neurologic outcome would be valuable tools for translational research.As such,the objective of the present review was to describe some of the translational challenges in acute spinal cord injury research and examine the potential utility of neurochemical biomarkers found within cerebrospinal fluid and blood.We focus on published efforts to establish biological markers for accurately classifying injury severity and precisely predict neurological outcome.展开更多
基金supported by the National Natural Science Foundation of China,No.81671819(to LKC)the Natural Science Foundation of Guangdong Province,Nos.2021A1515010001 and 2019A1515012103(both to LKC)。
文摘Our previo us study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes(hNSC-Exo)in ischemic stroke.Here,we loaded brain-derived neurotrophic factor(BDNF)into exosomes derived from NSCs to construct engineered exosomes(BDNF-hNSC-Exo)and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo.In a model of H_(2)O_(2)-induced oxidative stress in NSCs,BDNF-hNSC-Exo markedly enhanced cell survival.In a rat middle cerebral arte ry occlusion model,BDNF-hNSC-Exo not only inhibited the activation of microglia,but also promoted the differentiation of endogenous NSCs into neurons.These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stro ke.Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.
基金financially supported by the National Key Research and Development Program of China,No.2016YFC1100100(to XDG)
文摘Current management for spinal cord injury aims to reduce secondary damage and recover sensation and movement.Acute spinal cord injury is often accompanied by spinal cord compartment syndrome.Decompression by durotomy and/or myelotomy attempts to relieve secondary damage by completelyrelieving the compression of the spinal cord,removing the necrotic tissue,decreasing edema,reducing hemorrhage,and improving blood circulation in the spinal cord.However,it is controversial whether durotomy and/or myelotomy after spinal cord injury are beneficial to neurological recovery.This review compares the clinical effects of durotomy with those of myelotomy in the treatment of spinal cord injury.We found that durotomy has been performed more than myelotomy in the clinic,and that durotomy may be safer and more effective than myelotomy.Durotomy performed in humans had positive effects on neurological function in 92.3% of studies in this review,while durotomy in animals had positive effects on neurological function in 83.3% of studies.Myelotomy procedures were effective in 80% of animal studies,but only one clinical study of myelotomy has reported positive results,of motor and sensory improvement,in humans.However,a number of new animal studies have reported that durotomy and myelotomy are ineffective for spinal cord injury.More clinical data,in the form of a randomized controlled study,are needed to understand the effectiveness of durotomy and myelotomy.
基金supported by the National Natural Science Foundation of China,Nos.81871785 and 81672161(both to ZSY)。
文摘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.
基金This work was supported by the National Natural Science Foundation of China,No.81471308(to JL)Program of China National Health Commission and National Medical Products Administration(NMPA),No.CMR-20161129-1003(to JL)+1 种基金Liaoning Province Excellent Talent Program Project,No.XLYC1902031(to JL)Dalian Innovation Fund,No.2018J11CY025(to JL).
文摘Stroke is a main cause of death and disability worldwide.The ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that may give substantial and possibly complete recovery of brain function after stroke.Many animal models and clinical trials have demonstrated that neural stem cells(NSCs)in the central nervous system can orchestrate neurological repair through nerve regeneration,neuron polarization,axon pruning,neurite outgrowth,repair of myelin,and remodeling of the microenvironment and brain networks.Compared with other types of stem cells,NSCs have unique advantages in cell replacement,paracrine action,inflammatory regulation and neuroprotection.Our review summarizes NSC origins,characteristics,therapeutic mechanisms and repair processes,then highlights current research findings and clinical evidence for NSC therapy.These results may be helpful to inform the direction of future stroke research and to guide clinical decision-making.
文摘Stroke remains the leading cause of long-term disability.Hemiparesis is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor cortex.As the only direct descending motor pathway,the corticospinal tract(CST)is the primary pathway to innervate spinal motor neurons,and thus,forms the neuroanatomical basis to control the peripheral muscles for voluntary movements.Here,we review evidence from both experimental animals and stroke patients,regarding CST axonal damage,functional contribution of CST axonal integrity and remodeling to neurological recovery,and therapeutic approaches aimed to enhance CST axonal remodeling after stroke.The new insights gleaned from preclinical and clinical studies may encourage the development of more rational therapeutics with a strategy targeted to promote axonal rewiring for corticospinal innervation,which will significantly impact the current clinical needs of subacute and chronic stroke treatment.
基金supported by the National Natural Science Foundation of China,Nos.81801169 (to LXX),82071404 (to HC),81870952 (to HMW)。
文摘Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.
基金supported by the National Natural Science Foundation of China,No.81873317(to XJC),No.81704096(to MY),No.81603635(to JY)a grant from the Municipal Science and Technology Commission of Shanghai-TCM Key Project in China,No.16401970100(to YJW)+1 种基金a grant from the Shanghai TCM Medical Center of Chronic Disease in China,No.2017ZZ01010(to YJW)the National Thirteenth Five-Year Science and Technology Major Special Project for New Drug Innovation and Development in China,No.2017ZX09304001(to YJW)
文摘Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as the main search terms,all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed,EMBASE,MEDLINE,Web of Science,Science Direct,China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases by computer.The search was conducted from their inception date to April 2017.No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations.Two reviewers independently selected studies according to the title,abstract and full text.The risk of bias in the included studies was also evaluated.Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso,Beattie,and Bresnahan scale score,inclined plane score and Gale’s motor function score.Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels,malondialdehyde levels,nitric oxide synthase activity,nitric oxide levels,xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor.The results of meta-analysis showed that compared with the control group,resveratrol significantly increased the Basso,Beattie,and Bresnahan scale scores after spinal cord injury(n=300,mean difference(MD)=3.85,95%confidence interval(CI)[2.10,5.59],P<0.0001).Compared with the control group,superoxide dismutase levels were significantly elevated(n=138,standardized mean difference(SMD)=5.22,95%CI[2.98,7.45],P<0.00001),but malondialdehyde levels were significantly diminished(n=84,SMD=–3.64,95%CI[–5.84,–1.43],P=0.001)in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurologi
基金supported by the National Natural Science Foundation of China (81571596, 81601044, and 81771279)the National Basic Research Development Program of China (2017YFC1701300)Fundamental Research Funds for the Central Universities, China (GK201701009)
文摘Leukemia inhibitory factor(LIF) contributes to the neuroprotection by neural stem cells(NSCs) after ischemic stroke. Our aim was to explore whether LIFtransfected NSCs(LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro.Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion(MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injuryin the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.
基金supported by the National Natural Science Foundation of China,Nos.81601052(to XRJ),81520108017(to PFT)the Beijing Nova Program of Science and Technology of China,No.2018034(to XRJ)+1 种基金the Beijing Municipal Science and Technology Project of China,No.D16100002816005(to PFT)the Subsidiary of PLA Major Project of China,No.AWS17J004(to PFT)。
文摘Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits.In previous epidural electrical stimulation studies,single electrode sites and continuous tetanic stimulation have often been used.With this stimulation,the body is prone to declines in tolerance and locomotion coordination.In the present study,rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers,and were then subjected to epidural electrical stimulation.The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment.Simultaneously,the electrode stimulation site was able to be accurately applied to the L2–3 and S1 segments of the spinal cord.To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes,GFAP/Iba-1 doublelabeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation.Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation,and there was no activated Iba-1~+cell aggregation,indicating that the implant did not cause an inflammatory response in the spinal cord.Rat gait analysis showed that,at 3 days after surgery,gait became coordinated in rats with spinal cord injury under burst stimulation.The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution.To evaluate the matching degree between the flexible epidural electrode(including three stimulation contacts),vertebral morphology,and the level of the epidural site of the stimulation electrode,micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation.Based on the experimental results of gait recover
基金supported by Hong Kong Spinal Cord Injury Fund (HKSCIF),China (to HZ)。
文摘For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.
基金provided by the Rick Hansen InstituteMichael Smith Foundation for Health Research+1 种基金Craig Neilsen Foundationsupported by MITACS
文摘The evaluation of such novel therapies for acute spinal cord injury in clinical trials is extremely challenging.Our current dependence upon the clinical assessment of neurologic impairment renders many acute SCI patients ineligible for trials because they are not examinable.Furthermore,the difficulty in predicting neurologic recovery based on the early clinical assessment forces investigators to recruit large cohorts to have sufficient power.Biomarkers that objectively classify injury severity and better predict neurologic outcome would be valuable tools for translational research.As such,the objective of the present review was to describe some of the translational challenges in acute spinal cord injury research and examine the potential utility of neurochemical biomarkers found within cerebrospinal fluid and blood.We focus on published efforts to establish biological markers for accurately classifying injury severity and precisely predict neurological outcome.
