title: Drug-induced hypothermia as beneficial treatment before and after cerebral ischemia.
abstract: OBJECTIVE
  Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when conditioning before (preconditioning) and after (postconditioning) experimental stroke.
  
  
  METHODS
  Hypothermia was induced in rats with a bolus of 6 mg/kg talipexole followed by 20 h continuous talipexole infusion of 6 mg/kg in total. Controls received similar treatment with saline. The core body temperature was continuously monitored. In preconditioning, hypothermia was terminated before either reversible occlusion of the middle cerebral artery (MCAO) for 60 min or global ischemia for 10 min with 2-vessel occlusion and hypotension. In postconditioning, rats experienced 60 min of MCAO before hypothermia was induced either immediately or with 3 h delay. Rats survived ischemia for 2, 7 or 90 days. Infarct volumes were quantified by stereology. Additional experiments of methodological relevance were included in the study.
  
  
  RESULTS
  Talipexole induced mild hypothermia (35.1±1.1 to 36.0±0.5°C) for <20 h. Hypothermic pre- and postconditioning reduced infarct sizes by more than 60% as monitored during the first 90 days after experimental stroke (p<0.05).
  
  
  CONCLUSIONS
  Talipexole is registered for use as a dopamine substitute in humans with Parkinson's disease. Although dosages cannot be directly translated to patients, our study exemplifies in an animal model that drug-induced hypothermia in a clinical setting might reduce cerebral ischemic damage before neuro- and cardiac surgical procedures and after stroke.
authors.affiliation: Molecular Pathology, Biotech Research and Innovation Centre, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Flemming F
authors.initials: FF
authors.lastname: Johansen
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasseldam
authors.forename: Rune S
authors.initials: RS
authors.lastname: Rasmussen
authors.forename: Anne Sofie
authors.initials: AS
authors.lastname: Bisgaard
authors.forename: Peter K
authors.initials: PK
authors.lastname: Bonfils
authors.forename: Steen S
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Jacob
authors.initials: J
authors.lastname: Hansen-Schwartz
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D007036:Hypothermia, Induced / Q000379:methods*; D057775:Ischemic Postconditioning / Q000379:methods*; D019194:Ischemic Preconditioning / Q000379:methods*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D001381:Azepines; D018491:Dopamine Agonists; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C024763:talipexole