EFFECT OF HYPERTHERMIA ON GLUTAMATE RELEASE IN ISCHEMIC PENUMBRA AFTER MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Using microdialysis, we investigated the effect of hyperthermia on glutamate release in penumbral cortex of rats with 2 h of either normothermic (37 degrees C) or hyperthermic (39 degrees C) middle cerebral artery (MCA) occlusion. Penumbral blood flow (CBF) was measured by laser-Doppler flowmetry. CBF values (expressed as %preischemic values) in normothermic and hyperthermic groups were 24 +/- 11 (SD) and 24 +/- 16%, respectively, during ischemia and 102 +/- 81 and 147 +/- 79% during recirculation. Average extracellular glutamate in the hyperthermic group increased from a baseline of 7 +/- 2 mu M to a peak of 217 +/- 184 mu M at 10-20 min after onset of ischemia but returned to near baseline after 60 min. Glutamate in the normothermic group increased from 4 +/- 2 mu M to a peak of 26 +/- 17 mu M at 10-20 min after MCA occlusion but fell to near-baseline before recirculation. Thus reuptake systems appeared to remain functional in ischemic penumbra, even during hyperthermia. Ischemic glutamate release was significantly higher in hyperthermic than in normothermic rats: average values of individual rats' peak levels were 251 +/- 221 mu M and 37 +/- 34 mu M, respectively. The ischemic CBF threshold value for glutamate release was 33% of control in the normothermic group but 61% in the hyperthermic group.