Cj. Baker et al., INTRAISCHEMIC HYPOTHERMIA DECREASES THE RELEASE OF GLUTAMATE IN THE CORES OF PERMANENT FOCAL CEREBRAL INFARCTS, Neurosurgery, 36(5), 1995, pp. 994-1001
THE CEREBROPROTECTIVE EFFECTS of hypothermia in focal models of ischem
ia are well established, but little is known about the underlying mech
anisms of this form of brain protection. Cortical cooling in global tr
ansient ischemic models suggests that hypothermia limits glutamate exc
itotoxicity by decreasing the release of glutamate during ischemia. Fe
w studies have examined glutamate release in the more physiological mo
del 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 micr
odialysis for 30 minutes before MCAO to 120 minutes after MCAO. Normot
hermic animals (n = 13) had a baseline glutamate concentration of 9.23
+/- 2.5 mu mol/ml (mean +/- standard error of the mean) before MCAO.
Extracellular glutamate rose quickly after vessel occlusion and peaked
at 33.95 +/- 6.3 mu mol/ml 30 minutes after MCAO. By 60 minutes after
MCAO, this level had decreased to 25.14 +/- 6.3 mu mol/ml; glutamate
levels decreased slightly to 21.35 +/- 6.8 mu mol/ml by 120 minutes. H
ypothermic animals (n = 11) had an initial extracellular glutamate con
centration of 5.22 +/- 1.3 mu mol/ml before MCAO. This value rose grad
ually to a maximum of 10.69 +/- 3.3 mu m/ml at 50 minutes after MCAO a
nd then returned to a baseline value of 2.58 +/- 1.2 mu mol/ml by 120
minutes. Contralateral control glutamate dialysates in the normothermi
c and hypothermic groups remained near baseline throughout the experim
ental period. The mean percentages of right hemispheric volumes occupi
ed 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 cor
e glutamate may have implications for penumbral tissue viability.