• Daqing Ma, Peter Williamson, Adam Januszewski, Marie-Caroline Nogaro, Mahmuda Hossain, Lay Ping Ong, Yi Shu, Nicholas P Franks, and Mervyn Maze.
• Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, United Kingdom. d.ma@imperial.ac.uk
• Anesthesiology. 2007 Apr 1;106(4):746-53.

BackgroundAnesthetics, including isoflurane and nitrous oxide, an antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor, have been demonstrated to induce apoptotic neurodegeneration when administered during neurodevelopment. Xenon, also an N-methyl-D-aspartate antagonist, not only lacks the characteristic toxicity produced by other N-methyl-D-aspartate antagonists, but also attenuates the neurotoxicity produced by this class of agent. Therefore, the current study sought to investigate xenon's putative protective properties against anesthetic-induced neuronal apoptosis.MethodSeparate cohorts (n = 5 or 6 per group) of 7-day-old rats were randomly assigned and exposed to eight gas mixtures: air, 75% nitrous oxide, 75% xenon, 0.75% isoflurane, 0.75% isoflurane plus 35% or 75% nitrous oxide, 0.75% isoflurane plus 30% or 60% xenon for 6 h. Rats were killed, and cortical and hippocampal apoptosis was assessed using caspase-3 immunostaining. In separate cohorts, cortices were isolated for immunoblotting of caspase 3, caspase 8, caspase 9, and cytochrome c. Organotypic hippocampal slices of postnatal mice pups were derived and cultured for 24 h before similar gas exposures, as above, and subsequently processed for caspase-3 immunostaining.ResultsIn vivo administration of isoflurane enhances neuronal apoptosis. When combined with isoflurane, nitrous oxide significantly increases whereas xenon significantly reduces apoptosis to a value no different from that of controls. In vitro studies corroborate the ability of xenon to attenuate isoflurane-induced apoptosis. Isoflurane enhanced expression of indicators of the intrinsic and common apoptotic pathways; this enhancement was increased by nitrous oxide but attenuated by xenon.ConclusionsThe current study demonstrates that xenon prevents isoflurane-induced neonatal neuronal apoptosis.

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