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

Abstract

BACKGROUND:

Antagonists 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.

METHODS:

We 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.

RESULTS:

Xenon 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.

CONCLUSIONS:

Uniquely 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.

• Authors: D Ma, S Wilhelm, M Maze, N P Franks
• Journal: British journal of anaesthesia (Br J Anaesth) Vol. 89 Issue 5 Pg. 739-46 (Nov 2002) ISSN: 0007-0912 [Print] England
• PMID: 12393773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Neuroprotective Agents
• Proto-Oncogene Proteins c-fos
• Xenon
• N-Methylaspartate
• Ketamine
• Dizocilpine Maleate
• Haloperidol
• Nitrous Oxide

Topics

• Animals
• Arcuate Nucleus of Hypothalamus (drug effects, metabolism)
• Biomarkers (analysis)
• Brain (drug effects, metabolism)
• Brain Injuries (metabolism)
• Dizocilpine Maleate (pharmacology)
• Female
• Gene Expression (drug effects)
• Haloperidol (pharmacology)
• Ketamine (pharmacology, toxicity)
• Models, Animal
• N-Methylaspartate (metabolism)
• Neuroprotective Agents (pharmacology)
• Nitrous Oxide (pharmacology, toxicity)
• Proto-Oncogene Proteins c-fos (analysis)
• Rats
• Rats, Sprague-Dawley
• Xenon (pharmacology, toxicity)