• Br J Anaesth · Nov 2002

    Neuroprotective and neurotoxic properties of the 'inert' gas, xenon.

    • D Ma, S Wilhelm, M Maze, and N P Franks.
    • Magill Department of Anaesthesia, Chelsea and Westminster Hospital and Biophysics Group, The Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, UK.
    • Br J Anaesth. 2002 Nov 1;89(5):739-46.

    BackgroundAntagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors have been shown not only to have neuroprotective effects but also to exhibit neurotoxic properties. In this study, we used c-Fos, a protein product of an immediate early gene, as a marker of neuronal injury to compare the neuroprotective effects of xenon and the neurotoxic properties of xenon, nitrous oxide, and ketamine, three anaesthetics with NMDA receptor antagonist properties.MethodsWe used an in vivo rat model of brain injury in which N-methyl-DL-aspartic acid (NMA) is injected subcutaneously (s.c.) and c-Fos expression in the arcuate nucleus is used as a measure of injury. To examine the neurotoxic potential of each of the three anaesthetics with NMDA receptor antagonist properties, c-Fos expression in the posterior cingulate and retrosplenial (PC/RS) cortices was measured.ResultsXenon dose-dependently suppressed NMA-induced c-Fos expression in the arcuate nucleus with an IC(50) of 47 (2)% atm. At the highest concentration tested (75% atm) NMA-induced neuronal injury was decreased by as much as that observed with the prototypical NMDA antagonist MK801 (0.5 mg kg(-1) s.c.). Both nitrous oxide and ketamine dose-dependently increased c-Fos expression in PC/RS cortices; in contrast, xenon produced no significant effect. If the dopamine receptor antagonist haloperidol was given before either nitrous oxide or ketamine, their neurotoxic effects were eliminated.ConclusionsUniquely amongst anaesthetics with known NMDA receptor antagonist action, xenon exhibits neuroprotective properties without co-existing neurotoxicity. The reason why ketamine and nitrous oxide, but not xenon, produce neurotoxicity may involve their actions on dopaminergic pathways.

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