title: Glibenclamide is superior to decompressive craniectomy in a rat model of malignant stroke.
abstract: OBJECTIVE
  Treating patients with malignant cerebral infarctions remains a major unsolved problem in medicine. Decompressive craniectomy (DC) improves the bleak outlook but is suboptimal. Using a rat model of severe ischemia/reperfusion with very high mortality due to malignant cerebral edema, we tested the hypothesis that blocking of sulfonylurea receptor 1-regulated NC(Ca-ATP) channels with glibenclamide would compare favorably to DC when reperfusion and treatment were begun 6 hours after onset of ischemia.
  
  
  METHODS
  Male Wistar rats underwent filament occlusion of the middle cerebral artery to reduce laser Doppler flowmetry perfusion signals by >75%, with filament removal plus treatment 6 hours later. In rats treated with vehicle versus glibenclamide (10 microg/kg IP plus 200 ng/h SC), we compared mortality, neurologic function, and brain swelling at 24 hours. In rats treated with DC versus glibenclamide, we compared neurologic function for 2 weeks and histologic outcomes.
  
  
  RESULTS
  Compared with vehicle, glibenclamide treatment reduced 24-hour mortality from 67% to 5% and reduced hemispheric swelling at 24 hours from 21% to 8%. DC eliminated 24-hour mortality, but neurologic function during the next 2 weeks was significantly better with glibenclamide compared with DC. Watershed cortex and deep white matter were significantly better preserved with glibenclamide compared with DC.
  
  
  CONCLUSIONS
  In a rat model of severe ischemia/reperfusion, with reperfusion and treatment beginning 6 hours after onset of ischemia, glibenclamide is as effective as DC in preventing death from malignant cerebral edema but is superior to DC in preserving neurologic function and the integrity of watershed cortex and deep white matter.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA. msimard@smail.umaryland.edu
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.forename: Natalia
authors.initials: N
authors.lastname: Tsymbalyuk
authors.forename: Orest
authors.initials: O
authors.lastname: Tsymbalyuk
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ivanova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yurovsky
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
mesh_terms: D000818:Animals; D056424:Decompressive Craniectomy / Q000379:methods; D004195:Disease Models, Animal; D005905:Glyburide / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*
chemical_list: D005905:Glyburide