title: Xenon neurotoxicity in rat hippocampal slice cultures is similar to isoflurane and sevoflurane.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California at San Francisco, San Francisco, California 94143-0542, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Brosnan
authors.forename: Philip E
authors.initials: PE
authors.lastname: Bickler
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D014978:Xenon / Q000633:toxicity*
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D014978:Xenon; D007530:Isoflurane