Effects of Hypothermic Metabolic Suppression on Hippocampal Glutamate Concentrations After Transient Global Cerebral Ischemia

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Abstract
The cerebroprotective effects of mild and moderate hypothermia cannot be explained solely by a temperature-induced decrease in cerebral metabolic rate. This study examined the effects of graded hypothermia (32°C, 28°C, and 22°C, vs 38°C) on periischemic extracellular hippocampal glutamate concentrations in the New Zealand White rabbit. Global cerebral ischemia (15 min) was produced by a combination of neck tourniquet inflation and induction of systemic hypotension. Glutamate, an important mediator of ischemic neuronal injury, was measured using in vivo microdialysis and high-performance liquid chromatography. Mean extracellular glutamate concentrations increased by 11 μM in the 38°C group during the ischemic period. Glutamate increased by <1 μM in the 32°C and 28°C groups and by 3 μM in the 22°C group. Thus, mild degrees of hypothermia profoundly reduced glutamate release during ischemia. This reduction greatly exceeded the estimated temperature-induced decrease in cerebral metabolic rate. We conclude that hypothermic inhibition of glutamate release during episodes of transient ischemia may significantly contribute to neuronal protection.

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