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 degrees C, 28 degrees C, and 22 degrees C, vs 38 degrees 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 microM in the 38 degrees C group during the ischemic period.
Glutamate increased by < 1 microM in the 32 degrees C and 28 degrees C groups and by 3 microM in the 22 degrees 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.