VOLATILE AND INTRAVENOUS ANESTHETICS DECREASE GLUTAMATE RELEASE FROM CORTICAL BRAIN-SLICES DURING ANOXIA

Background: Extracellular accumulation of the excitatory neurotransmit ter L-glutamate during cerebral hypoxia or ischemia contributes to neu ronal death. Anesthetics inhibit release of synaptic neurotransmitters but it is unknown if they alter net extrasynaptic glutamate release, which accounts for most of the glutamate released during hypoxia or is chemia. The purpose of this study was to determine if different types of anesthetics decrease hypoxia-induced glutamate release from rat bra in slices. Methods: Glutamate released from cortical brain slices was measured fluorometrically with the glutamate dehydrogenase catalyzed f ormation of the reduced form of nicotinamide adenine dinucleotide phos phate from nicotinamide adenine dinucleotide phosphate. Glutamate rele ase was measured in oxygenated (Po-2 = 400 mmHg), hypoxic ((Po-2 = 20 mmHg), and anoxic ((Po-2 = 20 mmHg plus 100 mu M NaCN) solutions and w ith clinical concentrations of anesthetics (halothane 325 mu M, enflur ane 680 mu M, propofol 200 mu M, sodium thiopental 50 mu M). The sourc e of glutamate released during these stresses was defined with toxins inhibiting N and P type voltage-gated calcium channels, and with calci um-free medium. Results: Glutamate released during hypoxia or anoxia w as 1.5 and 5.3 times greater, respectively, than that evoked by depola rization with 30 mM KCl. Hypoxia/anoxia-induced glutamate release was not mediated by synaptic voltage-gated calcium channels, put probably by the reversal of normal uptake mechanisms, Halothane, enflurane, and sodium thiopental, but not propofol, decreased hypoxia-evoked glutama te release by 50-70% (P < 0.05). None of the anesthetics alter basal g lutamate release, Conclusions: The authors conclude that halothane, en flurane, and sodium thiopental but not propofol, at clinical concentra tions, decrease extrasynaptic release of L-glutamate during hypoxic st ress.