title: Adding 5 h delayed xenon to delayed hypothermia treatment improves long-term function in neonatal rats surviving to adulthood.
abstract: BACKGROUND
  We previously reported that combining immediate hypothermia with immediate or 2 h delayed inhalation of an inert gas, xenon, gave additive neuroprotection in rats after a hypoxic-ischemic insult, compared to hypothermia alone. Defining the therapeutic time window for this new combined intervention is crucial in clinical practice when immediate treatment is not always feasible. The aim of this study is to investigate whether combined hypothermia and xenon still provide neuroprotection in rats after a 5 h delay for both hypothermia and xenon.
  
  
  METHODS
  Seven-day-old Wistar rat pups underwent a unilateral hypoxic-ischemic insult. Pups received 5 h of treatment starting 5 h after the insult randomized between normothermia, hypothermia, or hypothermia with 50% xenon. Surviving pups were tested for fine motor function through weeks 8-10 before being euthanized at week 11. Their hemispheric and hippocampal areas were assessed.
  
  
  RESULTS
  Both delayed hypothermia-xenon and hypothermia-only treated groups had significantly less brain tissue loss than those which underwent normothermia. The functional performance after 1 wk and adulthood was significantly better after hypothermia-xenon treatment as compared to the hypothermia-only or normothermia groups.
  
  
  CONCLUSIONS
  Adding 50% xenon to 5 h delayed hypothermia significantly improved functional outcome as compared to delayed hypothermia alone despite similar reductions in brain area.
authors.affiliation: Department of Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Medicine, University of Wales Swansea, Swansea, UK.
authors.forename: John
authors.initials: J
authors.lastname: Dingley
authors.affiliation: Department of Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Scull-Brown
authors.affiliation: 1] Department of Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, UK [2] Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006624:Hippocampus / Q000473:pathology*; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D009048:Motor Skills / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013997:Time Factors; D014978:Xenon / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D014978:Xenon