Intraischemic Hypothermia Decreases the Release of Glutamate in the Cores of Permanent Focal Cerebral Infarcts

Abstract

THE CEREBROPROTECTIVE EFFECTS of hypothermia in focal models of ischemia are well established, but little is known about the underlying mechanisms of this form of brain protection. Cortical cooling in global transient ischemic models suggests that hypothermia limits glutamate excitotoxicity by decreasing the release of glutamate during ischemia. Few studies have examined glutamate release in the more physiological model of permanent focal ischemia. In this study, we used a rat model of middle cerebral artery occlusion (MCAO) of permanent focal ischemia. Extracellular glutamate concentration was analyzed bilaterally by microdialysis for 30 minutes before MCAO to 120 minutes after MCAO. Normothermic animals (n = 13) had a baseline glutamate concentration of 9.23 ± 2.5 μmol/ml (mean ± standard error of the mean) before MCAO. Extracellular glutamate rose quickly after vessel occlusion and peaked at 33.95 ± 6.3 μmol/ml 30 minutes after MCAO. By 60 minutes after MCAO, this level had decreased to 25.14 ± 6.3 μmol/ml; glutamate levels decreased slightly to 21.35 ± 6.8 μmol/ml by 120 minutes. Hypothermic animals (n = 11) had an initial extracellular glutamate concentration of 5.22 ± 1.3 μmol/ml before MCAO. This value rose gradually to a maximum of 10.69 ± 3.3 μm/ml at 50 minutes after MCAO and then returned to a baseline value of 2.58 ± 1.2 μmol/ml by 120 minutes. Contralateral control glutamate dialysates in the normothermic and hypothermic groups remained near baseline throughout the experimental period. The mean percentages of right hemispheric volumes occupied by infarcts were 11.96 ± 1.68% in the hypothermic group and 19.77 ± 2.03% in the normothermic animals. Hypothermia seems to decrease the peak and duration of extracellular glutamate efflux in the core of permanent focal infarcts. This decrease in the diffusable pool of core glutamate may have implications for penumbral tissue viability.