CRITICAL LEVELS OF EXTRACELLULAR GLUTAMATE MEDIATING GERBIL HIPPOCAMPAL DELAYED NEURONAL DEATH DURING HYPOTHERMIA - BRAIN MICRODIALYSIS STUDY

When the brain temperature was lowered by 2-degrees-C from normothermic temperature, a protective effect on postischemic neuronal death was exhibited and levels of extracellular glutamate were attenuated to about half of those at normothermic brain temperature in the gerbil hippocampus. Hypothermia has been reported to confer a protective effect on ischemia-induced delayed neuronal death. The present study was carried out to quantify this protective effect of hypothermia on the degree of alteration in extracellular release of glutamate during ischemia and the final histopathological outcome in the hippocampus. Extracellular glutamate levels were measured by microdialysis. In gerbils whose brain temperature was maintained at normothermia (37-degrees-C), glutamate increased during ischemia and the early period of recirculation (by 15-fold), and CA1 neurons were consistently damaged. In animals whose brain temperature was maintained at 35 or 33-degrees-C during ischemia, the release of glutamate was significantly attenuated to half of a quarter, respectively, at 37-degrees-C. In animals whose brain temperature was maintained at 31-degrees-C during ischemia, the release of glutamate was slightly lower than that at 33-degrees-C. No CA1 ischemic neuronal damage was seen in 60% of gerbils at 35-degrees-C and none was seen in any gerbils at 33 and 31-degrees-C. In animals whose brain temperature was maintained at 39-degrees-C during ischemia, the release of glutamate was slightly higher than that at 37-degrees-C, and a high mortality rate of animals (75%) was observed. Our results reinforce other recent evidence suggesting that one of the mechanisms by which lowering of the brain temperature by only a few degrees during ischemia exerts a protective effect in the hippocampus, involves the reduction of ischemia-induced glutamate release.