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

Background. Antagonists of the N-methyl-D-aspartate (NMDA) subtypeof glutamate receptors have been shown not only to have neuroprotectiveeffects 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 neuroprotectiveeffects of xenon and the neurotoxic properties of xenon, nitrousoxide, and ketamine, three anaesthetics with NMDA receptor antagonistproperties. Methods. We used an in vivo rat model of brain injury in whichN-methyl-DL-aspartic acid (NMA) is injected subcutaneously (s.c.)and c-Fos expression in the arcuate nucleus is used as a measureof injury. To examine the neurotoxic potential of each of thethree anaesthetics with NMDA receptor antagonist properties,c-Fos expression in the posterior cingulate and retrosplenial(PC/RS) cortices was measured. Results. Xenon dose-dependently suppressed NMA-induced c-Fosexpression in the arcuate nucleus with an IC₅₀ of 47 (2)% atm.At the highest concentration tested (75% atm) NMA-induced neuronalinjury was decreased by as much as that observed with the prototypicalNMDA antagonist MK801 (0.5 mg kg^–1 s.c.). Both nitrousoxide and ketamine dose-dependently increased c-Fos expressionin PC/RS cortices; in contrast, xenon produced no significanteffect. If the dopamine receptor antagonist haloperidol wasgiven before either nitrous oxide or ketamine, their neurotoxiceffects were eliminated. Conclusions. Uniquely amongst anaesthetics with known NMDA receptorantagonist action, xenon exhibits neuroprotective propertieswithout co-existing neurotoxicity. The reason why ketamine andnitrous oxide, but not xenon, produce neurotoxicity may involvetheir actions on dopaminergic pathways. Br J Anaesth 2002; 89: 739–46