Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain.
Anesthesiology
; 106(4): 746-53, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17413912
ABSTRACT
BACKGROUND:
Anesthetics, 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.METHOD:
Separate 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.RESULTS:
In 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.CONCLUSIONS:
The current study demonstrates that xenon prevents isoflurane-induced neonatal neuronal apoptosis.
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Base de dados:
MEDLINE
Assunto principal:
Xenônio
/
Encéfalo
/
Apoptose
/
Anestésicos Inalatórios
/
Isoflurano
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article