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

作者：Li Haopeng^*; Chen Jie; He Xijing; Xu Siyue; Liu Yu

来源：Neural Regeneration Research, 2009, 4(12): 979-985.

DOI：10.3969/j.issn.1673-5374.2009.12.003

• cauda equina syndrome
• p75 neurotrophin receptor
• spinal cord
• neurons
• apoptosis
• anterior horn

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, L(2-3) 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 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 of neurons in the L(2) 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 L(2-3) spinal cord segment.

• 出版日期2009-12
• 单位西安交通大学