Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are ...Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,we identify the challenges and possible solutions for spinal cord neuron imaging.展开更多
BACKGROUND： Studies have demonstrated that cauda equina compression results in apoptosis of motor neurons in the spinal cord. The combination of p75 neurotrophin receptor （p75NTR） and precursor of nerve growth fact...BACKGROUND： Studies have demonstrated that cauda equina compression results in apoptosis of motor neurons in the spinal cord. The combination of p75 neurotrophin receptor （p75NTR） and precursor of nerve growth factor （pro-NGF） expression initiates the apoptotic pathway and induces neuronal apoptosis. However, few reports have focused on the p75-mediated mechanism of neuronal apoptosis following cauda equine compression injury OBJECTIVE： To determine apoptosis of spinal cord neurons and activation of the pro-NGF-p75NTR-JNK（c-Jun N-terminal kinase） signal pathway in rats following cauda equina compression, and to verify experimental outcomes. DESIGN, TIME AND SETTING： A randomized, controlled, in vivo experiment was performed at the Medical Experimental Center of Xi＇an Jiaotong University between April and November in 2008. MATERIALS： Streptavidin-perosidase kit was purchased from Wuhan Boster, China; in situ end labeling detection kit was provided by Promega, USA; type AEG-220G electron microscope was purchased from Hitachi, Japan. METHODS： A total of 48 healthy, adult, female, Sprague Dawley rats were randomly assigned to three groups： normal （n = 6）, sham-surgery （n = 6）, and compression （n = 36）. The compression group was randomly assigned to six subsets at 1,3, 5, 7, 14, and 28 days, respectively, with 6 rats in each subset. A cylindrical silica gel stick was implanted into the rats to compress 75% of the vertebral canal in the compression group; in the sham-surgery group, only vertebral resection was performed; and no procedures were performed in the normal group. MAIN OUTCOME MEASURES： At 1,3, 5, 7, 14, and 28 days following compression, L2-3 spinal cord segments were processed for immunohistochemistry, in situ cell apoptosis detection, and transmission electron microscopy observation. Nissl staining was used to observe neuronal survival in the L2 spinal cord segment. Immunohistochemistry was applied to detect expressions of pro-NGF, p75NTR, and JNK in the L2 segment. TUNEL fluorometric method was used to observe apoptosis of neurons in the L2 segment. RESULTS： In the normal and sham-surgery groups, little neuronal apoptosis was observed in the L2-3 spinal cord segment. At 3 days after compression injury, pro-NGF, p75NTR and JNK expression was observed in the spinal cord. Expression levels reached a peak at 7 days, and then gradually decreased. In the compression and sham-surgery groups, neurons primarily expressed pro-NGF and p75NTR. The number of JNK-positive neurons in the compression group was dramatically increased compared with the sham-surgery group （P〈 0.05）. A few neurons were apoptotic in the spinal cord 1 day after compression injury. The number of apoptotic neurons gradually increased and reached a peak at 7 days, and subsequently decreased. Apoptosis was still detectable at 28 days. There was a positive correlation between p75NTR expression and neuronal apoptosis （r= 0.75, P〈 0.05）. CONCLUSION： Following cauda equina compression injury, apoptosis of spinal cord neurons was observed. The compression-induced neuronal apoptosis was associated with p75NTR expression in the L2-3 spinal cord segment.展开更多
Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesen- chymal stem cells in vivo remai...Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesen- chymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.展开更多
背景:肌萎缩型颈椎病治疗方法仍有争议。对于肌萎缩型颈椎病患者,保守治疗一般可以稳定或者改善症状,但无法治愈。进展性或严重的神经功能恶化的肌萎缩型颈椎病推荐手术治疗,但多数临床医师根据自己的临床经验选择手术方式,尚未达成统...背景:肌萎缩型颈椎病治疗方法仍有争议。对于肌萎缩型颈椎病患者,保守治疗一般可以稳定或者改善症状,但无法治愈。进展性或严重的神经功能恶化的肌萎缩型颈椎病推荐手术治疗,但多数临床医师根据自己的临床经验选择手术方式,尚未达成统一的标准或行业共识。不同分型的肌萎缩型颈椎病预后显著不同,可能影响手术方案选的选择。目的:通过对肌萎缩型颈椎病相关研究进行综述,总结并分析疾病发病机制、临床表现、分型、诊断、治疗和预后情况,以期为此病的临床治疗和手术方案选择提供参考。方法:通过计算机检索1952-2020年发表在PubMed、EMbase、Web of Science、中国知网和万方数据库的肌萎缩型颈椎病相关研究文章,选择符合纳入标准的44篇文献进行综述。结果与结论:(1)肌萎缩型颈椎病的临床表现以上肢运动无力伴有明显的肌肉萎缩,而下肢没有明显的感觉障碍或痉挛性麻痹为特征,具有不对称性、节段性等特点;(2)临床多采用依据肌肉萎缩位置的不同进行分型,分为近端型、远端型和混合型,该疾病需与运动神经元病、肌肉营养不良疾病相鉴别,避免误诊和误治;(3)目前关于肌萎缩型颈椎病的发病机制尚不清楚,有腹侧神经根和脊髓前角细胞损伤两种观点,后者得到大部分学者认可;(4)肌萎缩型颈椎病的诊断主要依据临床症状、影像学检查及神经电生理检查,鉴别诊断上主要需排除运动神经元病等;(5)肌萎缩型颈椎病的治疗以手术为主,颈椎前路前路手术是治疗首选,而对于多节段颈椎后纵韧带骨化、前路不可能减压或者减压风险太大的患者需选择后路手术;(6)不同类型肌萎缩型颈椎病患者术后取得的预后效果有一定差异,其中近端型较远端型预后效果更佳,混合型预后最差,颈椎前路较后路手术效果佳。展开更多
基金supported by the National Natural Science Foundation of China,No.82272478(to PT)。
文摘Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,we identify the challenges and possible solutions for spinal cord neuron imaging.
基金the National Natural Science Foundation of China, No. 30672136
文摘BACKGROUND： Studies have demonstrated that cauda equina compression results in apoptosis of motor neurons in the spinal cord. The combination of p75 neurotrophin receptor （p75NTR） and precursor of nerve growth factor （pro-NGF） expression initiates the apoptotic pathway and induces neuronal apoptosis. However, few reports have focused on the p75-mediated mechanism of neuronal apoptosis following cauda equine compression injury OBJECTIVE： To determine apoptosis of spinal cord neurons and activation of the pro-NGF-p75NTR-JNK（c-Jun N-terminal kinase） signal pathway in rats following cauda equina compression, and to verify experimental outcomes. DESIGN, TIME AND SETTING： A randomized, controlled, in vivo experiment was performed at the Medical Experimental Center of Xi＇an Jiaotong University between April and November in 2008. MATERIALS： Streptavidin-perosidase kit was purchased from Wuhan Boster, China; in situ end labeling detection kit was provided by Promega, USA; type AEG-220G electron microscope was purchased from Hitachi, Japan. METHODS： A total of 48 healthy, adult, female, Sprague Dawley rats were randomly assigned to three groups： normal （n = 6）, sham-surgery （n = 6）, and compression （n = 36）. The compression group was randomly assigned to six subsets at 1,3, 5, 7, 14, and 28 days, respectively, with 6 rats in each subset. A cylindrical silica gel stick was implanted into the rats to compress 75% of the vertebral canal in the compression group; in the sham-surgery group, only vertebral resection was performed; and no procedures were performed in the normal group. MAIN OUTCOME MEASURES： At 1,3, 5, 7, 14, and 28 days following compression, L2-3 spinal cord segments were processed for immunohistochemistry, in situ cell apoptosis detection, and transmission electron microscopy observation. Nissl staining was used to observe neuronal survival in the L2 spinal cord segment. Immunohistochemistry was applied to detect expressions of pro-NGF, p75NTR, and JNK in the L2 segment. TUNEL fluorometric method was used to observe apoptosis of neurons in the L2 segment. RESULTS： In the normal and sham-surgery groups, little neuronal apoptosis was observed in the L2-3 spinal cord segment. At 3 days after compression injury, pro-NGF, p75NTR and JNK expression was observed in the spinal cord. Expression levels reached a peak at 7 days, and then gradually decreased. In the compression and sham-surgery groups, neurons primarily expressed pro-NGF and p75NTR. The number of JNK-positive neurons in the compression group was dramatically increased compared with the sham-surgery group （P〈 0.05）. A few neurons were apoptotic in the spinal cord 1 day after compression injury. The number of apoptotic neurons gradually increased and reached a peak at 7 days, and subsequently decreased. Apoptosis was still detectable at 28 days. There was a positive correlation between p75NTR expression and neuronal apoptosis （r= 0.75, P〈 0.05）. CONCLUSION： Following cauda equina compression injury, apoptosis of spinal cord neurons was observed. The compression-induced neuronal apoptosis was associated with p75NTR expression in the L2-3 spinal cord segment.
基金supported by Scientific Research Fund of Xinxiang Medical University,No.2013ZD120Science and Technology Innovation Talents in Universities in Ministry of Education of Henan Province in 2010,No.2010HASTIT036
文摘Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesen- chymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.
文摘背景:肌萎缩型颈椎病治疗方法仍有争议。对于肌萎缩型颈椎病患者,保守治疗一般可以稳定或者改善症状,但无法治愈。进展性或严重的神经功能恶化的肌萎缩型颈椎病推荐手术治疗,但多数临床医师根据自己的临床经验选择手术方式,尚未达成统一的标准或行业共识。不同分型的肌萎缩型颈椎病预后显著不同,可能影响手术方案选的选择。目的:通过对肌萎缩型颈椎病相关研究进行综述,总结并分析疾病发病机制、临床表现、分型、诊断、治疗和预后情况,以期为此病的临床治疗和手术方案选择提供参考。方法:通过计算机检索1952-2020年发表在PubMed、EMbase、Web of Science、中国知网和万方数据库的肌萎缩型颈椎病相关研究文章,选择符合纳入标准的44篇文献进行综述。结果与结论:(1)肌萎缩型颈椎病的临床表现以上肢运动无力伴有明显的肌肉萎缩,而下肢没有明显的感觉障碍或痉挛性麻痹为特征,具有不对称性、节段性等特点;(2)临床多采用依据肌肉萎缩位置的不同进行分型,分为近端型、远端型和混合型,该疾病需与运动神经元病、肌肉营养不良疾病相鉴别,避免误诊和误治;(3)目前关于肌萎缩型颈椎病的发病机制尚不清楚,有腹侧神经根和脊髓前角细胞损伤两种观点,后者得到大部分学者认可;(4)肌萎缩型颈椎病的诊断主要依据临床症状、影像学检查及神经电生理检查,鉴别诊断上主要需排除运动神经元病等;(5)肌萎缩型颈椎病的治疗以手术为主,颈椎前路前路手术是治疗首选,而对于多节段颈椎后纵韧带骨化、前路不可能减压或者减压风险太大的患者需选择后路手术;(6)不同类型肌萎缩型颈椎病患者术后取得的预后效果有一定差异,其中近端型较远端型预后效果更佳,混合型预后最差,颈椎前路较后路手术效果佳。
