Role of Glibenclamide in Brain Injury After Intracerebral Hemorrhage

Bing Jiang, Lin Li, Qianwei Chen, Yihao Tao, Liming Yang, Bo Zhang, John H. Zhang, Hua Feng, Zhi Chen, Jun Tang, Gang Zhu

Research output: Contribution to journalArticlepeer-review

Abstract

Brain edema following intracerebral hemorrhage (ICH) causes severe secondary brain injury, and no efficient pharmacological preventions are available. The present study was designed to demonstrate the neuroprotective effects of glibenclamide on brain edema and key factors of the blood–brain barrier (BBB). The study was divided into two parts. First, we utilized an autoblood-induced rat model to investigate the expression of sulfonylurea receptor 1 (Sur1). Second, rats were randomized into sham, vehicle, and glibenclamide groups. Neurological scores, brain water content, Evans blue extravasation, Morris water maze test, western blots, and immunofluorescence were used to study the effects of glibenclamide. The expression of the Sur1-Trpm4 channel but not the Sur1-KATP channel was increased in the perihematomal tissue following ICH. Glibenclamide administration significantly decreased the brain water content, restored the BBB, and reduced the expression of MMPs. In addition, glibenclamide improved long-term cognitive deficits following ICH. Glibenclamide protected BBB integrity and improved neurological outcomes after ICH by inhibiting the Sur1-Trpm4 channel, which reduces the expression of MMPs and thereby increases BBB tight-junction protein levels. Glibenclamide may have potential to protect the BBB after ICH.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalTranslational Stroke Research
Volume8
Issue number2
DOIs
StatePublished - Apr 1 2017

ASJC Scopus Subject Areas

  • General Neuroscience
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Keywords

  • BBB
  • Glibenclamide
  • Intracerebral hemorrhage
  • MMPs
  • Sur1
  • Matrix Metalloproteinase 2/metabolism
  • Occludin/metabolism
  • Sulfonylurea Receptors/agonists
  • Matrix Metalloproteinase 9/metabolism
  • Blood Glucose/metabolism
  • Potassium Channels, Inwardly Rectifying/metabolism
  • Rats
  • Male
  • Endothelium/drug effects
  • Rats, Sprague-Dawley
  • Cerebral Hemorrhage/complications
  • Glyburide/administration & dosage
  • Brain Edema/etiology
  • Animals
  • Zonula Occludens-1 Protein/metabolism
  • Blood-Brain Barrier/drug effects
  • TRPM Cation Channels/metabolism
  • Maze Learning/drug effects

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