With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because o...With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.展开更多
Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury...Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli（ST36）,Xuanzhong（GB39）,Futu（ST32）and Sanyinjiao（SP6）were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase（ACh E）activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor（GDNF）m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.展开更多
Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods...Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).展开更多
Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbili...Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia.The ability of OECs to migrate is unknown,especially in hypoxic conditions,and the effect of OECs combined with exosomes on peripheral nerve repair is not clear.Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed.In this study,OECs were acquired from the olfactory bulb of Sprague Dawley rats.Human umbilical cord mesenchymal stem cell-derived exosomes(0–400μg/mL)were cultured with OECs for 12–48 hours.After culture with 400μg/mL exosomes for 24 hours,the viability and proliferation of OECs were significantly increased.We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes.Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions,and effectively increased brain-derived neurotrophic factor gene expression,protein levels and secretion.Finally,using a 12 mm left sciatic nerve defect rat model,we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve.These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery.This study was approved by the Institutional Ethical Committee of the Air Force Medical University,China(approval No.IACUC-20181004)on October 7,2018;and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital,China(approval No.30054)on May 20,2019.展开更多
Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated fac...Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.展开更多
Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cell...Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.展开更多
Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the aut...Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine（3-MA） in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA（3 mg/kg） 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium（LiCl; 30 mg/kg） 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3 B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3 B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN＋ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.展开更多
The protective effects of erythropoietin on spinal Here, the eukaryotic expression plasmid pcDNA3.1 cord injury have not been well described. human erythropoietin was transfected into rat neural stem cells cultured in...The protective effects of erythropoietin on spinal Here, the eukaryotic expression plasmid pcDNA3.1 cord injury have not been well described. human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was inject- ed with non-transfected neural stem cells. Dulbecco＇s modified Eagle＇s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem ceils group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bd-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythro- poietin-neural stem cells group. At 4 weeks, the somatosensory evoked potential latencies were cavities were clearly smaller and the motor and remarkably shorter in the human erythropoi- etin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythro- poietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the subarachnoid cavity to help repair spinal cord展开更多
基金supported by the Key Laboratory of Trauma and Neural Regeneration (Peking University),Ministry of Education of China,No. BMU2020XY005-03National Natural Science Foundation of China,No. 31771322+2 种基金Beijing Science&Technology New Star Cross Project of China,No. 201819Major R&D Program of National Ministry of Science and Technology of China,No. 2018YFB1105504a grant from National Center for Trauma Medicine,Beijing,China,No. BMU2020XY005-01 (all to PXZ)。
文摘With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.
基金supported by a grant from the Shaanxi Province Scientific and Technological Project in China,No.2014TM4193
文摘Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli（ST36）,Xuanzhong（GB39）,Futu（ST32）and Sanyinjiao（SP6）were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase（ACh E）activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor（GDNF）m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.11672332(to XYC)the National Key Research and Development Plan of China,No.2016YFC1101500(to SZ)
文摘Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord.Indeed,cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration.This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord.This scaffold allows cell growth in vitro and in vivo.To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury.Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed),spinal cord injury (transection injury of T10 spinal cord without any transplantation),3D-CF (3D scaffold was transplanted into the local injured cavity),and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity.Neuroelectrophysiology,imaging,hematoxylin-eosin staining,argentaffin staining,immunofluorescence staining,and western blot assay were performed.Apart from the sham group,neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups.Moreover,latency of the 3D-CF + NSCs group was significantly reduced,while the amplitude was significantly increased in motor evoked potential tests.The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group.Moreover,regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups.These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord.This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No.2017-0007.2).
基金supported by grants from the National Natural Science Foundation of China,No.81872699(to MS)Key project of Shaanxi Province,China,No.2017ZDXM-SF-043(to MS)the Military Medical Science and Technology Youth Development Program,China,No.19QNP061(to CL)
文摘Olfactory ensheathing cells(OECs)are promising seed cells for nerve regeneration.However,their application is limited by the hypoxic environment usually present at the site of injury.Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia.The ability of OECs to migrate is unknown,especially in hypoxic conditions,and the effect of OECs combined with exosomes on peripheral nerve repair is not clear.Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed.In this study,OECs were acquired from the olfactory bulb of Sprague Dawley rats.Human umbilical cord mesenchymal stem cell-derived exosomes(0–400μg/mL)were cultured with OECs for 12–48 hours.After culture with 400μg/mL exosomes for 24 hours,the viability and proliferation of OECs were significantly increased.We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes.Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions,and effectively increased brain-derived neurotrophic factor gene expression,protein levels and secretion.Finally,using a 12 mm left sciatic nerve defect rat model,we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve.These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery.This study was approved by the Institutional Ethical Committee of the Air Force Medical University,China(approval No.IACUC-20181004)on October 7,2018;and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital,China(approval No.30054)on May 20,2019.
基金supported by the National Natural Science Foundation of China,No. 82001604 (to LLX)the Joint Subject of Southwest Medical University and Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University of China,No. 2018XYLH-004 (to LLX)+1 种基金the National Construction Project of Regional Chinese Medicine Treatment Centre of China,No. 2018205 (to XB)the National Construction Project of the Second Clinical Research Base of Chinese Medicine of China,No. 2018131 (to XB)。
文摘Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.
基金This work was also supported by the National Natural Science Foundation of China,No.81901365(to WRQ)Jilin Science and Technology Agency Funds in China,Nos.20180101118JC(to RL),20180520115JH(to BPC)and 20190103076JH(to WRQ).
文摘Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.
基金supported by the Beijing Excellent Talent Training Funding in China,No.2017000021469G215(to DZ)the Youth Science Foundation of Beijing Tiantan Hospital of China,No.2016-YQN-14(to DZ)+1 种基金the Natural Science Foundation of Capital Medical University of China,No.PYZ2017082(to DZ)the Xi’an Science and Technology Project in China,No.2016048SF/YX04(3)(to XHL)
文摘Lithium promotes autophagy and has a neuroprotective effect on spinal cord injury（SCI）; however, the underlying mechanisms remain unclear. Therefore, in this study, we investigated the effects of lithium and the autophagy inhibitor 3-methyladenine（3-MA） in a rat model of SCI. The rats were randomly assigned to the SCI, lithium, 3-MA and sham groups. In the 3-MA group, rats were intraperitoneally injected with 3-MA（3 mg/kg） 2 hours before SCI. In the lithium and 3-MA groups, rats were intraperitoneally injected with lithium（LiCl; 30 mg/kg） 6 hours after SCI and thereafter once daily until sacrifice. At 2, 3 and 4 weeks after SCI, neurological function and diffusion tensor imaging indicators were remarkably improved in the lithium group compared with the SCI and 3-MA groups. The Basso, Beattie and Bresnahan locomotor rating scale score and fractional anisotropy values were increased, and the apparent diffusion coefficient value was decreased. Immunohistochemical staining showed that immunoreactivities for Beclin-1 and light-chain 3 B peaked 1 day after SCI in the lithium and SCI groups. Immunoreactivities for Beclin-1 and light-chain 3 B were weaker in the 3-MA group than in the SCI group, indicating that 3-MA inhibits lithium-induced autophagy. Furthermore, NeuN＋ neurons were more numerous in the lithium group than in the SCI and 3-MA groups, with the fewest in the latter. Our findings show that lithium reduces neuronal damage after acute SCI and promotes neurological recovery by inducing autophagy. The neuroprotective mechanism of action may not be entirely dependent on the enhancement of autophagy, and furthermore, 3-MA might not completely inhibit all autophagy pathways.
基金supported by the Science and Technology Development Program of Jilin Province of China,No.2011084
文摘The protective effects of erythropoietin on spinal Here, the eukaryotic expression plasmid pcDNA3.1 cord injury have not been well described. human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was inject- ed with non-transfected neural stem cells. Dulbecco＇s modified Eagle＇s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1-4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem ceils group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bd-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythro- poietin-neural stem cells group. At 4 weeks, the somatosensory evoked potential latencies were cavities were clearly smaller and the motor and remarkably shorter in the human erythropoi- etin-neural stem cells group and neural stem cells group than those in the spinal cord injury group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythro- poietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the subarachnoid cavity to help repair spinal cord
