title: Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.
abstract: BACKGROUND
  Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval.
  
  
  METHODS
  Rats were subjected to 70 min temporary focal ischemia. Ninety minutes later, rats were treated with 0, 15, 30, or 45% Xe for 20 h or 0 or 30% Xe for 8, 20, or 44 h. Outcome was measured after 7 days. In another experiment, after ischemia, rats were maintained at 37.5° or 36.0°C for 20 h with or without 30% Xe. Outcome was assessed 28 days later. Finally, mice were subjected to intracerebral hemorrhage with or without 30% Xe for 20 h. Brain water content, hematoma volume, rotarod function, and microglial activation were measured.
  
  
  RESULTS
  Cerebral infarct sizes (mean±SD) for 0, 15, 30, and 45% Xe were 212±27, 176±55, 160±32, and 198±54 mm, respectively (P=0.023). Neurologic scores (median±interquartile range) followed a similar pattern (P=0.002). Infarct size did not vary with treatment duration, but neurologic score improved (P=0.002) at all xenon exposure durations (8, 20, and 44 h). Postischemic treatment with either 30% Xe or subtherapeutic hypothermia (36°C) had no effect on 28-day outcome. Combination of these interventions provided long-term benefit. Xenon improved intracerebral hemorrhage outcome measures.
  
  
  CONCLUSIONS
  Xenon improved focal ischemic outcome at 7, but not 28 days postischemia. Xenon combined with subtherapeutic hypothermia produced sustained recovery benefit. Xenon improved intracerebral hemorrhage outcome. Xenon may have potential for clinical stroke therapy under carefully defined conditions.
authors.affiliation: University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Siyuan P
authors.initials: SP
authors.lastname: Sheng
authors.forename: Beilei
authors.initials: B
authors.lastname: Lei
authors.forename: Michael L
authors.initials: ML
authors.lastname: James
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lascola
authors.forename: Talaignair N
authors.initials: TN
authors.lastname: Venkatraman
authors.forename: Jin Yong
authors.initials: JY
authors.lastname: Jung
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Franks
authors.forename: Robert D
authors.initials: RD
authors.lastname: Pearlstein
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010865:Pilot Projects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000473:pathology / Q000628:therapy*; D014978:Xenon / Q000008:administration & dosage*
chemical_list: D018696:Neuroprotective Agents; D014978:Xenon