Neuroprotective potential of glibenclamide is mediated by antioxidant and anti-apoptotic pathways in intracerebral hemorrhage

Brain Res Bull. 2018 Sep:142:18-24. doi: 10.1016/j.brainresbull.2018.06.006. Epub 2018 Jun 19.

Abstract

The sulfonylurea receptor 1 (SUR1)-regulated NCca-ATP channels were progressively upregulated and demonstrated unchecked opening in central nervous system (CNS) injury, which induced cerebral damage. Glibenclamide (GLI) can block NCca-ATP channels and consequently exert protective effects. Recent studies have found that GLI has antioxidative effects. In this study, we primarily explored the antioxidative effects of GLI in a rat model of intracerebral hemorrhage (ICH). We found that GLI could scavenge free radicals, reduce activated-caspase-3 expression, increase the Bcl-2/Bax ratio, inhibit apoptosis, and improve functional neurological outcomes in a rat model of ICH.

Keywords: Apoptosis; Glibenclamide; Intracerebral hemorrhage; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Caspase 3 / metabolism
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / pathology
  • Disease Models, Animal
  • Free Radicals / metabolism
  • Glyburide / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Random Allocation
  • Rats
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Bax protein, rat
  • Bcl2 protein, rat
  • Free Radicals
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Casp3 protein, rat
  • Caspase 3
  • Glyburide