Delayed paraplegia after spinal cord ischemic injury requires caspase-3 activation in mice.
Delayed paraplegia after spinal cord ischemic injury requires caspase-3 activation in mice.
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DOI：
10.1161/strokeaha.110.600429
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发表时间：
2011-08
期刊：
影响因子：
8.3
通讯作者：
Ichinose F
中科院分区：
文献类型：
--
作者：
Kakinohana M;Kida K;Minamishima S;Atochin DN;Huang PL;Kaneki M;Ichinose F
迟发性截瘫仍然是与主动脉手术和创伤相关的缺血性脊髓损伤后的毁灭性并发症。虽然细胞凋亡与迟发性神经变性的发病机制有关，但造成迟发性截瘫的机制仍不完全清楚。本研究的目的是阐明细胞凋亡在脊髓缺血后迟发性运动神经元变性中的作用。小鼠因主动脉弓和左锁骨下动脉闭塞5或9分钟而诱发脊髓缺血。脊髓缺血后 72 小时内评估后肢运动功能。进行组织学研究以检测连续脊髓切片中的 caspase-3 激活、神经胶质激活和运动神经元存活。为了研究 caspase-3 激活对脊髓缺血的影响，在缺乏 caspase-3 的小鼠中检查了脊髓缺血的结果。在野生型小鼠中，9分钟的脊髓缺血导致立即截瘫，而5分钟的脊髓缺血则导致迟发性截瘫。脊髓缺血 5 分钟后的迟发性截瘫与脊髓缺血后 24-48 小时左右开始的 caspase-3 激活、反应性星形胶质细胞增生、小胶质细胞激活和运动神经元丢失的组织学证据相关。 Caspase-3 缺乏可以预防脊髓缺血 5 分钟后的迟发性截瘫和运动神经元丧失，但不能预防缺血 9 分钟后的立即截瘫。目前的结果表明，脊髓缺血后迟发性截瘫和运动神经元变性需要 caspase-3 激活。
Delayed paraplegia remains a devastating complication after ischemic spinal cord injury associated with aortic surgery and trauma. While apoptosis has been implicated in the pathogenesis of delayed neurodegeneration, mechanisms responsible for the delayed paraplegia remain incompletely understood. The aim of this study was to elucidate the role of apoptosis in delayed motor neuron degeneration after spinal cord ischemia. Mice were subjected to spinal cord ischemia induced by occlusion of the aortic arch and left subclavian artery for 5 or 9 min. Motor function in the hind limb was evaluated up to 72h after spinal cord ischemia. Histological studies were performed to detect caspase-3 activation, glial activation, and motor neuron survival in the serial spinal cord sections. To investigate the impact of caspase-3 activation on spinal cord ischemia, outcome of the spinal cord ischemia was examined in mice deficient for caspase-3. In wild-type mice, 9 min of spinal cord ischemia caused immediate paraplegia, whereas 5 min of ischemia caused delayed paraplegia. Delayed paraplegia after 5 min of spinal cord ischemia was associated with histological evidence of caspase-3 activation, reactive astrogliosis, microglial activation, and motor neuron loss starting around 24–48h after spinal cord ischemia. Caspase-3 deficiency prevented delayed paraplegia and motor neuron loss after 5 min of spinal cord ischemia, but not immediate paraplegia after 9 min of ischemia. The present results suggest that caspase-3 activation is required for delayed paraplegia and motor neuron degeneration after spinal cord ischemia.