title: Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methyl-D-aspartate receptor glycine site.
abstract: BACKGROUND
  Xenon, the inert anesthetic gas, is neuroprotective in models of brain injury. The authors investigate the neuroprotective mechanisms of the inert gases such as xenon, argon, krypton, neon, and helium in an in vitro model of traumatic brain injury.
  
  
  METHODS
  The authors use an in vitro model using mouse organotypic hippocampal brain slices, subjected to a focal mechanical trauma, with injury quantified by propidium iodide fluorescence. Patch clamp electrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate receptors and TREK-1 channels, two molecular targets likely to play a role in neuroprotection.
  
  
  RESULTS
  Xenon (50%) and, to a lesser extent, argon (50%) are neuroprotective against traumatic injury when applied after injury (xenon 43±1% protection at 72 h after injury [N=104]; argon 30±6% protection [N=44]; mean±SEM). Helium, neon, and krypton are devoid of neuroprotective effect. Xenon (50%) prevents development of secondary injury up to 48 h after trauma. Argon (50%) attenuates secondary injury, but is less effective than xenon (xenon 50±5% reduction in secondary injury at 72 h after injury [N=104]; argon 34±8% reduction [N=44]; mean±SEM). Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitive inhibition at the N-methyl-D-aspartate receptor glycine site mediating xenon neuroprotection against traumatic brain injury. Xenon inhibits N-methyl-D-aspartate receptors and activates TREK-1 channels, whereas argon, krypton, neon, and helium have no effect on these ion channels.
  
  
  CONCLUSIONS
  Xenon neuroprotection against traumatic brain injury can be reversed by increasing the glycine concentration, consistent with inhibition at the N-methyl-D-aspartate receptor glycine site playing a significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.
authors.affiliation: * Ph.D. Student, † Masters Student, ‡ Professor of Biophysics and Anaesthetics, § Lecturer in Anaesthetics, Anaesthetics, Pain Medicine, and Intensive Care Section, Department of Surgery and Cancer, Biophysics Section, Imperial College London, London, United Kingdom.
authors.forename: Katie
authors.initials: K
authors.lastname: Harris
authors.forename: Scott P
authors.initials: SP
authors.lastname: Armstrong
authors.forename: Rita
authors.initials: R
authors.lastname: Campos-Pires
authors.forename: Louise
authors.initials: L
authors.lastname: Kiru
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Franks
authors.forename: Robert
authors.initials: R
authors.lastname: Dickinson
mesh_terms: D000399:Air Pressure; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001128:Argon / Q000494:pharmacology*; D001273:Atmosphere Exposure Chambers; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000293:injuries / Q000473:pathology; D002452:Cell Count; D002460:Cell Line; D055724:Electrophysiological Phenomena; D005998:Glycine / Q000187:drug effects* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents; D009924:Organ Culture Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014978:Xenon / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D024683:Potassium Channels, Tandem Pore Domain; D016194:Receptors, N-Methyl-D-Aspartate; C103742:potassium channel protein TREK-1; D014978:Xenon; D001128:Argon; D005998:Glycine