Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Stroke. 2011 Aug;42(8):2302-7. doi: 10.1161/STROKEAHA.110.600429. Epub 2011 Jun 23.
Delayed paraplegia remains a devastating complication after ischemic spinal cord injury associated with aortic surgery and trauma. Although 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 minutes. Motor function in the hind limb was evaluated up to 72 hours 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 minutes of spinal cord ischemia caused immediate paraplegia, whereas 5 minutes of ischemia caused delayed paraplegia. Delayed paraplegia after 5 minutes of spinal cord ischemia was associated with histological evidence of caspase-3 activation, reactive astrogliosis, microglial activation, and motor neuron loss starting at approximately 24 to 48 hours after spinal cord ischemia. Caspase-3 deficiency prevented delayed paraplegia and motor neuron loss after 5 minutes of spinal cord ischemia, but not immediate paraplegia after 9 minutes of ischemia.
The present results suggest that caspase-3 activation is required for delayed paraplegia and motor neuron degeneration after spinal cord ischemia.
与主动脉手术和创伤相关的缺血性脊髓损伤后，迟发性截瘫仍然是一种毁灭性的并发症。尽管凋亡已被牵涉到迟发性神经退行性变的发病机制中，但导致迟发性截瘫的机制仍不完全清楚。本研究的目的是阐明凋亡在脊髓缺血后迟发性运动神经元退化中的作用。
通过阻断主动脉弓和左锁骨下动脉 5 或 9 分钟来诱导脊髓缺血。在脊髓缺血后，对后肢的运动功能进行评估，直至 72 小时。在连续脊髓切片中检测半胱天冬酶-3 激活、神经胶质激活和运动神经元存活，以进行组织学研究。为了研究半胱天冬酶-3 激活对脊髓缺血的影响，在缺乏半胱天冬酶-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 分钟的缺血导致迟发性截瘫。5 分钟脊髓缺血后的迟发性截瘫与半胱天冬酶-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，始于脊髓缺血后约 24 至 48 小时。半胱天冬酶-3 缺乏可预防 5 分钟脊髓缺血后的迟发性截瘫和运动神经元丢失，但不能预防 9 分钟缺血后的立即截瘫。
本研究结果表明，半胱天冬酶-3 激活是脊髓缺血后迟发性截瘫和运动神经元退化所必需的。
