Ischemic tolerance after spinal cord ischemia

我们研究了短暂的脊髓缺血和随后的严重缺血损伤之间的间隔对后肢运动功能和脊髓组织病理学的影响。为探讨脊髓缺血耐受的机制，采用异氟醚麻醉，阻断腹主动脉，造成脊髓短暂缺血，观察70-kDa热休克蛋白（HSP70）的诱导作用。短暂缺血后，脊髓节段诱发电位第三负波消失时开始再循环。这种缺血性损伤并没有在脊髓中产生神经元损伤。在第一次缺血后2天、4天或7天（每组n = 8），动物（双缺血组）经受第二次缺血20分钟。单次缺血组接受假手术代替第一次缺血，并在假手术后4天同样进行第二次缺血。第二次缺血后2天，评价后肢运动功能。脊髓灌流固定后，计数腰髓前部正常神经元，首次缺血后4d再次缺血的双缺血组动物的神经功能状态和组织病理学均明显优于单缺血组。脊髓短暂缺血后2、4、7天诱导HSP70表达。脊髓缺血再灌注后4h，所有神经功能正常的动物均可见HSP70的强阳性染色，提示脊髓缺血再灌注后4d可观察到缺血耐受，而2、7d则不能充分观察到缺血耐受，提示HSP70以外的因素可能在脊髓缺血耐受机制中起重要作用。

We investigated the effect of interval between brief spinal cord ischemia and subsequent severe ischemic insult on hindlimb motor function and histopathology of the spinal cord. To explore the mechanism of spinal ischemic tolerance, induction of 70- kDa heat shock protein (HSP70) was also evaluated.A brief spinal cord ischemia was produced by occlusion of the abdominal aorta during isoflurane anesthesia. Recirculation after brief ischemia was started when the third negative wave of segmental spinal cord evoked potential disappeared. This ischemic insult did not produce neuronal damage in the spinal cord. Two days, 4 days, or 7 days (n=8 in each) following the first ischemia, the animals (double ischemia group) were subjected to the second ischemia for 20 minutes. The single ischemia group received a sham procedure instead of the first ischemia and was identically subjected to the second ischemia 4 days following the sham procedure. Two days following the second ischemia, hindlimb motor function was evaluated. After perfusion and fixation of the spinal cord, normal neurons in the anterior lumber spinal cord were counted.The neurologic status and histopathology in the animals in the double ischemia group subjected to the second ischemia 4 days after first ischemia were significantly better than in the single ischemia group. HSP70 was induced 2 days, 4 days, and 7 days after brief spinal cord ischemia. Intense HSP70 staining was observed 4 hours after second ischemic insult in all animals that showed normal neurologic function regardless of preconditioning with brief spinal cord ischemia.These results suggest that ischemic tolerance was observed 4 days, but not adequately 2 or 7 days after brief spinal cord ischemia and that factors other than HSP70 may play an important role in the mechanism of spinal ischemic tolerance.