The effect of Na(+)/H(+) exchanger-1 inhibition by sabiporide on blood-brain barrier dysfunction after ischemia/hypoxia in vivo and in vitro

Brain Res. 2010 Dec 17:1366:189-96. doi: 10.1016/j.brainres.2010.09.077. Epub 2010 Sep 29.

Abstract

In the present study, we investigated the effects of sabiporide, a specific NHE-1 inhibitor, on blood-brain barrier (BBB) endothelial dysfunction during ischemia/hypoxia in rat cerebral ischemia in vivo and bEnd.3 cells in vitro. Sabiporide significantly attenuated ischemia/hypoxia-induced BBB hyperpermeability and disruption of occludin and zonula occludens-1 both in vivo and in vitro. Sabiporide also inhibited the hypoxia-induced increase in [Ca(2+)](i) in bEnd.3 cells. Taken together, the protective effect of sabiporide on BBB permeability may be mediated through maintaining tight junction integrity and associated with its inhibitory effect on [Ca(2+)](i) overload under hypoxia. These results suggest that the BBB protective effect of sabiporide may be of therapeutical benefit in brain injury after an ischemic stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / physiopathology
  • Brain / cytology
  • Calcium / metabolism
  • Carbon Isotopes / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / therapeutic use*
  • Evans Blue
  • Gene Expression / drug effects
  • Guanidines / therapeutic use*
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology*
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Neuroglia / drug effects
  • Neuroglia / physiology
  • Occludin
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Hydrogen Exchangers / antagonists & inhibitors*
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism
  • Sucrose / metabolism
  • Tight Junctions / genetics
  • Tight Junctions / metabolism

Substances

  • Carbon Isotopes
  • Cytoskeletal Proteins
  • Enzyme Inhibitors
  • Guanidines
  • Membrane Proteins
  • Occludin
  • Ocln protein, mouse
  • Ocln protein, rat
  • RNA, Messenger
  • Sodium-Hydrogen Exchangers
  • growth factor-activatable Na-H exchanger NHE-1
  • Evans Blue
  • Sucrose
  • Calcium
  • sabiporide