The long-term effects of post-ischemic hypothermia on neuronal survival

采用沙鼠全脑缺血实验研究了缺血后低温对神经元存活的长期影响。缺血后立即在32℃x 4hr进行低温治疗。缺血后1周和1个月分别进行形态学、生物学和功能检查。缺血后低温可在1周内阻止缺血细胞死亡，但缺血后1个月时，缺血后低温的保护作用程度降低。低温后，部分神经元死亡，DNA断裂。免疫组织化学和原位杂交均显示海马n -甲基- d -天冬氨酸受体（NMDAR）异常，缺血1周后长时程增强也被抑制。MK-801是一种非竞争性NMDAR拮抗剂，可预防缺血性低体温后的慢性细胞死亡。在沙鼠缺血1个月后，经MK-801低温治疗后，沙鼠八臂根治性试验的表现得到了很好的维持，但不仅仅是低温。这些结果提示一些谷氨酸受体的异常可能是由缺血引起的；尽管低温治疗，这种异常仍会持续存在，导致慢性细胞死亡。部分神经元死亡与细胞凋亡有关。缺血后低温和MK-801联合使用有助于保护神经元免受缺血损伤。

The long-term effects of post-ischemic hypothermia on neuronal survival were investigated using global ischemia in gerbils. Hypothermia was induced at 32 ℃ x 4hr immediately after ischemia. Morphological, biological, and functional examinations were performed at 1 week and 1 month after ischemia. Post-ischemic hypothermia prevented ischemic cell death at 1 week, however, the degree of protective effect of post-ischemic hypothermia was reduced at 1 month after ischemia. Some neurons were dead with DNA fragmentation after hypothermia. Both immunohistochemistry and in situ hybridization showed abnormality of N-methyl-D-aspartate receptor (NMDAR) in the hippocampus, and long-term potentiation was also depressed at 1 week after ischemia. The administration of MK-801, which is a non-competitive NMDAR antagonist, prevented the chronic cell death after post-ischemic hypothermia. The performance of eight-arm radical trial in gerbils was well maintained at 1 month after ischemia by the hypothermia with MK-801 treatment, but not only hypothermia. These results suggest that some abnormalities in the glutamate receptor may be caused by ischemia; such abnormality would persist in spite of hypothermia treatment, resulting in the chronic cell death. Some neurons were dead associated with apoptosis. The combination of post-ischemic hypothermia and administration of MK-801 is useful for neuronal protection against ischemic insult.