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

缺血后低温对神经元存活的长期影响

基本信息

批准号：
11680757
负责人：
MIYAMOTO Osamu
金额：
$ 2.37万
依托单位：
Kagawa Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680757/
关键词：
Hypothermia Cerebral ischemia Apoptosis MK-801 NMDA recepor Combination therapy Hippocampus Neuronal cell death グルタミン酸受容体砂ネズミ前脳虚血 AMPA受容体 RT-PCR 長期増強 8方向迷路慢性的な細胞死

项目摘要

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.

采用沙土鼠全脑缺血模型，研究缺血后低温对神经元存活的长期影响。缺血后立即在32 ℃ × 4小时诱导低温。分别于缺血后1周和1个月进行形态学、生物学和功能学检查。缺血后低温在1周时阻止了缺血性细胞死亡，然而，缺血后低温的保护作用程度在缺血后1个月时降低。低温后部分神经元死亡，DNA断裂。免疫组化和原位杂交均显示缺血1周海马N-甲基-D-天冬氨酸受体（NMDAR）异常，长时程增强也受到抑制。MK-801是一种非竞争性NMDAR拮抗剂，可预防缺血后低温后的慢性细胞死亡。缺血后1个月，MK-801治疗的低温可良好地维持沙土鼠八臂根治性试验的性能，但不仅是低温。这些结果表明，谷氨酸受体的一些异常可能是由缺血引起的，这种异常将持续存在，尽管低温治疗，导致慢性细胞死亡。部分神经元死亡，伴有细胞凋亡。缺血后低温和MK-801给药的组合可用于保护神经元免受缺血性损伤。