title: Xenon improves neurologic outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury.
abstract: OBJECTIVE
  To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury and to determine whether application of xenon has a clinically relevant therapeutic time window.
  
  
  METHODS
  Controlled animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male C57BL/6N mice (n = 196).
  
  
  METHODS
  Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact.
  
  
  RESULTS
  Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor function and gait. Our study shows that xenon treatment improves outcome following traumatic brain injury. Neurologic outcome scores were significantly (p < 0.05) better in xenon-treated groups in the early phase (24 hr) and up to 4 days after injury. Contusion volume was significantly (p < 0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p < 0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 or 3 hours after injury. Neurologic outcome was significantly (p < 0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p < 0.05) were observed in the xenon-treated group, 1 month after trauma.
  
  
  CONCLUSIONS
  These results show for the first time that xenon improves neurologic outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in patients with brain trauma.
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, Imperial College London, United Kingdom.
authors.forename: Rita
authors.initials: R
authors.lastname: Campos-Pires
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, Imperial College London, United Kingdom.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Armstrong
authors.affiliation: Department of Anaesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Sebastiani
authors.affiliation: Department of Anaesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Luh
authors.affiliation: Department of Anaesthesiology, Klinikum Hanau, Hanau, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Gruss
authors.affiliation: Mouse Behavioral Outcome Unit, Focus Program Translational Neurosciences (FTN), Johannes Gutenberg University, Mainz, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Radyushkin
authors.affiliation: Department of Anaesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hirnet
authors.affiliation: Department of Anaesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.affiliation: Department of Anaesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelhard
authors.affiliation: Department of Life Sciences, Imperial College London, United Kingdom.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Franks
authors.affiliation: Department of Anaesthesiology, Medical Center of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Serge C
authors.initials: SC
authors.lastname: Thal
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, Imperial College London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Dickinson
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005684:Gait / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014978:Xenon / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D014978:Xenon