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

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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.