title: Hypothermia ameliorates ischemic brain damage and suppresses the release of extracellular amino acids in both normo- and hyperglycemic subjects.
abstract: It has previously been shown that hypothermia markedly reduces cellular release of the excitatory amino acid glutamate and ameliorates ischemic damage. Based on extensive data showing that preischemic hyperglycemia exaggerates brain damage due to transient forebrain ischemia we posed the question whether glutamate release during ischemia in hyperglycemic rats is attenuated or prevented by induced hypothermia, and if such attenuation/prevention correlates with amelioration of the characteristic brain damage observed in hyperglycemic subjects. The experiments were performed in rats subjected to a 15-min period of forebrain ischemia, plasma glucose concentration being maintained at approximately 5 mM (control) or approximately 20 mM (hyperglycemia) prior to ischemia. Extracellular amino acid concentrations were measured by HPLC techniques on microdialysis samples which were collected from left dorsal hippocampus and right neocortex, and tissue damage was assessed by histopathology. Hypothermia (30 degrees C), which was induced 45 min prior to ischemia, reduced the neuronal damage not only in the ischemia-vulnerable regions but also in the normally ischemia-resistant areas that are recruited in the damage process in hyperglycemic subjects. The extracellular glutamate concentration was markedly increased in response to the ischemic insult in normothermic-normoglycemic animals. The concentration of glutamate was further increased in normothermic-hyperglycemic animals. Hypothermia inhibited the rise in glutamate concentrations, as well as in the concentrations of other excitatory and inhibitory amino acids. It is discussed whether hypothermia reduces the hyperglycemia-mediated damage by inhibiting extracellular glutamate release during an ischemic transient.
authors.affiliation: Saskatchewan Stroke Research Centre, University of Saskatchewan, Saskatoon, Canada.
authors.forename: P A
authors.initials: PA
authors.lastname: Li
authors.forename: Q P
authors.initials: QP
authors.lastname: He
authors.forename: H
authors.initials: H
authors.lastname: Miyashita
authors.forename: W
authors.initials: W
authors.lastname: Howllet
authors.forename: B K
authors.initials: BK
authors.lastname: Siesjö
authors.forename: A
authors.initials: A
authors.lastname: Shuaib
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006943:Hyperglycemia / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism*; D008297:Male; D016548:Prosencephalon / Q000098:blood supply* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000032:analysis
chemical_list: D018846:Excitatory Amino Acids; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid