Hypothermia ameliorates ischemic brain damage and suppresses the release of extracellular amino acids in both normo and hyperglycemic subjects

It has previously been shown that hypothermia markedly reduces cellular rel ease of the excitatory amino acid glutamate and ameliorates ischemic damage . Based on extensive data showing that preischemic hyperglycemia exaggerate s brain damage due 60 transient forebrain ischemia we posed the question wh ether glutamate release during ischemia in hyperglycemic rats is attenuated or prevented by induced hypothermia, and if such attenuation/prevention co rrelates with amelioration of the characteristic brain damage observed in h yperglycemic subjects. The experiments were performed in rats subjected to a 15-min period of forebrain ischemia, plasma glucose concentration being m aintained at similar to 5 mM (control) or similar to 20 mM (hyperglycemia) prior to ischemia. Extracellular amino acid concentrations were measured by HPLC techniques on microdialysis samples which were collected from left do rsal hippocampus and right neocortex, and tissue damage was assessed by his topathology. Hypothermia (30 degrees C), which was induced 45 min prior 60 ischemia, reduced the neuronal damage not only in the ischemia-vulnerable r egions but also in the normally ischemia-resistant areas that are recruited in the damage process in hyperglycemic subjects. The extracellular glutama te concentration was markedly increased in response to the ischemic insult in normothermic-normoglycemic animals. The concentration of glutamate was f urther increased in normothermic-hyperglycemic animals. Hypothermia inhibit ed the rise in glutamate concentrations, as well as in the concentrations o f other excitatory and inhibitory amino acids. It is discussed whether hypo thermia reduces the hyperglycemia-mediated damage by inhibiting extracellul ar glutamate release during an ischemic transient. (C) 1999 Academic Press.