title: Glibenclamide Improves Survival and Neurologic Outcome After Cardiac Arrest in Rats.
abstract: OBJECTIVE
  Glibenclamide confers neuroprotection in animal models as well as in retrospective clinical studies. This study determines whether glibenclamide improves outcome after cardiac arrest in rats.
  
  
  METHODS
  Prospective randomized laboratory study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 126).
  
  
  METHODS
  Rats successfully resuscitated from 8-minute asphyxial cardiac arrest were randomized to glibenclamide or vehicle group. Rats in the glibenclamide group were intraperitoneally administered glibenclamide with a loading dose of 10 μg/kg at 10 minutes and a maintenance dose of 1.2 μg at 6, 12, 18, and 24 hours after return of spontaneous circulation, whereas rats in the vehicle group received equivalent volume of vehicle solution.
  
  
  RESULTS
  Survival was recorded every day, and neurologic deficit scores were assessed at 24, 48, and 72 hours and 7 days after return of spontaneous circulation (n = 22 in each group). Results showed that glibenclamide treatment increased 7-day survival rate, reduced neurologic deficit scores, and prevented neuronal loss in the hippocampal cornu ammonis 1 region. To investigate the neuroprotective effects of glibenclamide in acute phase, we observed neuronal injury at 24 hours after return of spontaneous circulation and found that glibenclamide significantly decreased the rate of neuronal necrosis and apoptosis. In addition, glibenclamide reduced the messenger RNA expression of tumor necrosis factor-α and monocyte chemoattractant protein-1 in the cortex after return of spontaneous circulation. Furthermore, the sulfonylurea receptor 1 and transient receptor potential M4 heteromers, the putative therapeutic targets of glibenclamide, were up-regulated after cardiac arrest and cardiopulmonary resuscitation, indicating that they might be involved in neuroprotective effect of glibenclamide.
  
  
  CONCLUSIONS
  Glibenclamide treatment substantially improved survival and neurologic outcome throughout a 7-day period after return of spontaneous circulation. The salutary effects of glibenclamide were associated with suppression of neuronal necrosis and apoptosis, as well as inflammation in the brain.
authors.affiliation: All authors: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Kaibin
authors.initials: K
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Yafang
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ji
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wang
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Lin
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Zuoshan
authors.initials: Z
authors.lastname: Xie
authors.forename: Suyue
authors.initials: S
authors.lastname: Pan
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005905:Glyburide / Q000494:pharmacology*; D006323:Heart Arrest / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011446:Prospective Studies; D012333:RNA, Messenger; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D064233:Sulfonylurea Receptors / Q000378:metabolism; D050053:TRPM Cation Channels / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C577509:Abcc8 protein, rat; D018932:Chemokine CCL2; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D064233:Sulfonylurea Receptors; D050053:TRPM Cation Channels; C500239:TRPM4 protein, rat; D014409:Tumor Necrosis Factor-alpha; D005905:Glyburide