HYPOTHERMIA AND ISOFLURANE SIMILARLY INHIBIT GLUTAMATE RELEASE EVOKEDBY CHEMICAL ANOXIA IN RAT CORTICAL BRAIN-SLICES

Background: Accumulation of the excitatory neurotransmitter glutamate in ischemic brain tissue contributes to neuronal cell death. Volatile anesthetics at clinically relevant concentrations are neuroprotective in tn vivo models of brain ischemia and reduce glutamate release in vi vo and in vitro but they appear to have weaker neuroprotective effects than hypothermia. The purpose of this study was to determine whether isoflurane reduces glutamate release in hypoxic brain slices, how larg e this effect is compared to that of hypothermia, and if it is diminis hed by hyperthermia, Methods: Glutamate released from rat cortical bra in slices during chemical anoxia (100 mu M NaCN) was measured continuo usly with a fluorescence assay, The release rate was compared at three temperatures (28 degrees C, 37 degrees C, and 39 degrees C) with and without isoflurane at concentrations equipotent to 1 minimum alveolar concentration. At the same three temperatures, glutamate release rates before and after exposure to isoflurane were compared. Results: Isofl urane reduced glutamate release from brain slices during chemical anox ia at 37 degrees C (19.6%, P < 0.01) and at 39 degrees C (25.4%, P < 0 .01), but not at 28 degrees C., The reduction in glutamate release wit h hypothermia was similar to that with isoflurane. Hyperthermia (39 de grees C) caused greater glutamate release under basal and anoxic condi tions than normo- and hypothermia, Isoflurane caused a slight increase in basal glutamate release rates, although this effect was smaller th an the increase caused by hyperthermia. Conclusions: In a brain slice model of cerebral anoxia, 1 minimum alveolar concentration isoflurane decreases glutamate release to a similar extent that hypothermia (28 d egrees C) does, The increased glutamate release with hyperthermia (39 degrees C) is not prevented by isoflurane.