Hypothermia and isoflurane similarly inhibit glutamate release evoked by 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 in vivo models of brain ischemia and reduce glutamate release in vivo 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 large this effect is compared to that of hypothermia, and if it is diminished by hyperthermia.


METHODS
Glutamate released from rat cortical brain slices during chemical anoxia (100 microM NaCN) was measured continuously 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
Isoflurane reduced glutamate release from brain slices during chemical anoxia 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 with hypothermia was similar to that with isoflurane. Hyperthermia (39 degrees C) caused greater glutamate release under basal and anoxic conditions than normo- and hypothermia. Isoflurane caused a slight increase in basal glutamate release rates, although this effect was smaller than 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 degrees C) does. The increased glutamate release with hyperthermia (39 degrees C) is not prevented by isoflurane.
Eilers
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Department of Anesthesia, University of California School of Medicine, San Francisco 94143-0542, USA. eilers@jemo.ucsf.edu
Bickler
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D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
D018685:Anesthetics, Inhalation; D018698:Glutamic Acid; D007530:Isoflurane