MILD HYPOTHERMIA REDUCES PENUMBRAL GLUTAMATE LEVELS IN THE RAT PERMANENT FOCAL CEREBRAL-ISCHEMIA MODEL

ALTHOUGH THE CEREBROPROTECTIVE effects of hypothermia in focal models of ischemia are undisputed, the underlying mechanisms of this protecti on are still subject to much controversy. To analyze whether mild hypo thermia attenuates glutamate levels in the penumbra surrounding perman ent focal infarcts, extracellular glutamate concentration was analyzed bilaterally by microdialysis 20 minutes before to 120 minutes after a middle cerebral artery occlusion (MCAO) in rats. Normothermic animals (n = 11) had a baseline glutamate concentration of 1.14 +/- 0.40 mu m ol/ml (standard error of the mean) before the MCAO. Extracellular glut amate levels increased gradually after vessel occlusion to peak at 10. 1 +/- 1.45 mu mol/ml 80 minutes after the MCAO. This level gradually d ecreased to 5.72 +/- 1.67 mu mol/ml by 120 minutes. Hypothermic animal s (n = 11) had a baseline glutamate concentration of 1.73 +/- 0.83 mu mol/ml before the MCAO. Extracellular glutamate levels increased after vessel occlusion but stabilized at 3.47 +/- 1.37 mu mol/ml 30 minutes after the MCAO and remained stable until completion of the experiment . There were no significant differences in cortical blood flow between the normothermic and hypothermic groups at any time during the experi ment. Infarct volumes, expressed as a percentage of the volume of the right (ipsilateral) hemisphere, were 19.8 +/- 2.16% in the normothermi c group and 13.0 +/- 1.42% in the hypothermic group (P < 0.02). Althou gh the normothermic penumbral glutamate levels began to increase immed iately after the MCAO, they did not peak until 80 minutes after occlus ion. In contrast, the normothermic core glutamate levels peaked within 30 minutes after the MCAO. Glutamate diffusion from the core region t o the penumbra might account for this delay. Hypothermic cerebroprotec tion might involve a reduction in the pool of potentially diffusable g lutamate in the core region but have little direct effect on glutamate release in the penumbra.