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p75 neurotrophin receptor signal pathway influence on apoptosis in anterior horn neurons of the spinal cord in a rat model of cauda equina compression injury

查看全文 作  者:Haopeng Li Jie Chen Xijing He Siyue Xu Yu [1]Liu 高影响力作者 机构地区:[1]Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China高影响力机构 出  处:《Neural Regeneration Research》索引2009年第4卷第12期,共7页高影响力期刊 基  金:the National Natural Science Foundation of China, No. 30672136 摘  要:BACKGROUND: Studies have demonstrated that cauda equina compression results in apoptosis ofmotor neurons in the spinal cord. The combination of p75 neurotrophin receptor (p75NTR) andprecursor of nerve growth factor (pro-NGF) expression initiates the apoptotic pathway and inducesneuronal apoptosis. However, few reports have focused on the p75-mediated mechanism ofneuronal apoptosis following cauda equine compression injuryOBJECTIVE: To determine apoptosis of spinal cord neurons and activation of thepro-NGF-p75NTR-JNK(c-Jun N-terminal kinase) signal pathway in rats following cauda equinacompression, and to verify experimental outcomes.DESIGN, TIME AND SETTING: A randomized, controlled, in vivo experiment was performed at theMedical 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 endlabeling detection kit was provided by Promega, USA; type AEG-220G electron microscope waspurchased from Hitachi, Japan.METHODS: A total of 48 healthy, adult, female, Sprague Dawley rats were randomly assigned tothree groups: normal (n = 6), sham-surgery (n = 6), and compression (n = 36). The compressiongroup was randomly assigned to six subsets at 1,3, 5, 7, 14, and 28 days, respectively, with 6 rats ineach subset. A cylindrical silica gel stick was implanted into the rats to compress 75% of thevertebral canal in the compression group; in the sham-surgery group, only vertebral resection wasperformed; and no procedures were performed in the normal group.MAIN OUTCOME MEASURES: At 1,3, 5, 7, 14, and 28 days following compression, L_(2-3) spinalcord segments were processed for immunohistochemistry, in situ cell apoptosis detection, andtransmission electron microscopy observation. Nissl staining was used to observe neuronal survivalin the L_2 spinal cord segment. Immunohistochemistry was applied to detect expressions of pro-NGF,p75NTR, and JNK in the L_2 segment. TUNEL fluorometric method was used to observe apoptosis ofneurons in the L_2 segment.RESULTS: In the normal and sham-surgery groups, little neuronal apoptosis was observed in theL_(2-3) spinal cord segment. At 3 days after compression injury, pro-NGF, p75NTR and JNK expressionwas observed in the spinal cord. Expression levels reached a peak at 7 days, and then graduallydecreased. In the compression and sham-surgery groups, neurons primarily expressed pro-NGFand p75NTR. The number of JNK-positive neurons in the compression group was dramaticallyincreased compared with the sham-surgery group (P < 0.05). A few neurons were apoptotic in thespinal cord 1 day after compression injury. The number of apoptotic neurons gradually increasedand reached a peak at 7 days, and subsequently decreased. Apoptosis was still detectable at 28days. 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 wasobserved. The compression-induced neuronal apoptosis was associated with p75NTR expression inthe L_(2-3) spinal cord segment. 关 键 词:神经细胞凋亡 P75NTR 神经营养素受体 脊髓神经元 压缩损伤 信号通路 大鼠模型 神经营养因子
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