Volatile and intravenous anesthetics decrease glutamate release from cortical brain slices during anoxia.
BACKGROUND
Extracellular accumulation of the excitatory neurotransmitter L-glutamate during cerebral hypoxia or ischemia contributes to neuronal 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 ischemia. The purpose of this study was to determine if different types of anesthetics decrease hypoxia-induced glutamate release from rat brain slices.


METHODS
Glutamate released from cortical brain slices was measured fluorometrically with the glutamate dehydrogenase catalyzed formation of the reduced form of nicotinamide adenine dinucleotide phosphate. Glutamate release was measured in oxygenated (PO2 = 400 mmHg), hypoxic ((PO2 = 20 mmHg), and anoxic ((PO2 = 20 mmHg plus 100 microM NaCN) solutions and with clinical concentrations of anesthetics (halothane 325 microM, enflurane 680 microM, propofol 200 microM, sodium thiopental 50 microM). The source of glutamate released during these stresses was defined with toxins inhibiting N and P type voltage-gated calcium channels, and with calcium-free medium.


RESULTS
Glutamate released during hypoxia or anoxia was 1.5 and 5.3 times greater, respectively, than that evoked by depolarization with 30 mM KCl. Hypoxia/anoxia-induced glutamate release was not mediated by synaptic voltage-gated calcium channels, but probably by the reversal of normal uptake mechanisms. Halothane, enflurane, and sodium thiopental, but not propofol, decreased hypoxia-evoked glutamate release by 50-70% (P < 0.05). None of the anesthetics alter basal glutamate release.


CONCLUSIONS
The authors conclude that halothane, enflurane, and sodium thiopental but not propofol, at clinical concentrations, decrease extrasynaptic release of L-glutamate during hypoxic stress.
Department of Anesthesia, University of California School of Medicine, San Francisco 94143-0542, USA.
P E
PE
Bickler
L T
LT
Buck
J R
JR
Feiner
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004737:Enflurane / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013874:Thiopental / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D018698:Glutamic Acid; D004737:Enflurane; D013874:Thiopental; D006221:Halothane; D015742:Propofol