Xenon Neurotoxicity in Rat Hippocampal Slice Cultures Is Similar to Isoflurane and Sevoflurane

BACKGROUND:Anesthetic neurotoxicity in the developing brain of rodents and primates has raised concern. Xenon may be a nonneurotoxic alternative to halogenated anesthetics, but its toxicity has only been studied at low concentrations, where neuroprotective effects predominate in animal models. An eq...

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Bibliographic Details
Published in:Anesthesiology (Philadelphia) 2013-08, Vol.119 (2), p.335-344
Main Authors: Brosnan, Heather, Bickler, Philip E
Format: Article
Language:English
Subjects:
Alveoli
Anesthesia
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Anesthetics, Inhalation - toxicity
Animals
Animals, Newborn
Biological and medical sciences
Cell Death - drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Hippocampus - drug effects
Isoflurane - toxicity
Male
Medical sciences
Methyl Ethers - toxicity
Neurons - drug effects
Organ Culture Techniques
Primates
Rats
Rats, Sprague-Dawley
Xenon - toxicity
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Summary:BACKGROUND:Anesthetic neurotoxicity in the developing brain of rodents and primates has raised concern. Xenon may be a nonneurotoxic alternative to halogenated anesthetics, but its toxicity has only been studied at low concentrations, where neuroprotective effects predominate in animal models. An equipotent comparison of xenon and halogenated anesthetics with respect to neurotoxicity in developing neurons has not been made. METHODS:Organotypic hippocampal cultures from 7-day-old rats were exposed to 0.75, 1, and 2 minimum alveolar concentrations (MAC) partial pressures (60% xenon at 1.2, 2.67, and 3.67 atm; isoflurane at 1.4, 1.9, and 3.8%; and sevoflurane at 3.4 and 6.8%) for 6 h, at atmospheric pressure or in a pressure chamber. Cell death was assessed 24 h later with fluorojade and fluorescent dye exclusion techniques. RESULTS:Xenon caused death of hippocampal neurons in CA1, CA3, and dentate regions after 1 and 2 MAC exposures, but not at 0.75 MAC. At 1 MAC, xenon increased cell death 40% above baseline (P < 0.01; ANOVA with Dunnett test). Both isoflurane and sevoflurane increased neuron death at 1 but not 2 MAC. At 1 MAC, the increase in cell death compared with controls was 63% with isoflurane and 90% with sevoflurane (both P < 0.001). Pretreatment of cultures with isoflurane (0.75 MAC) reduced neuron death after 1 MAC xenon, isoflurane, and sevoflurane. CONCLUSION:Xenon causes neuronal cell death in an in vitro model of the developing rodent brain at 1 MAC, as does isoflurane and sevoflurane at similarly potent concentrations. Preconditioning with a subtoxic dose of isoflurane eliminates this toxicity.
ISSN:0003-3022
1528-1175
DOI:10.1097/ALN.0b013e31829417f0