Blockade of the mitochondrial permeability transition pore diminishes infarct size in the rat after transient middle cerebral artery occlusion

J Cereb Blood Flow Metab. 1999 Jul;19(7):736-41. doi: 10.1097/00004647-199907000-00002.

Abstract

The mitochondrial permeability transition pore is an inducer of cell death. During the reperfusion phase after cerebral ischemia, calcium accumulates in mitochondria, and a burst of free radical formation occurs, conditions that favor the activation of the mitochondrial permeability transition pore. Here the authors demonstrate that a blocker of the mitochondrial permeability transition pore, the nonimmunosuppressive cyclosporin A analogue N-methyl-Val-4-cyclosporin A (10 mg/kg intraperitoneally), administered during reperfusion and at 24 hours of reperfusion, diminishes infarct size in a rat model of transient focal ischemia of 2 hours' duration. The mitochondrial permeability transition pore may be an important target for drugs against stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane Permeability / drug effects
  • Cerebral Arteries / pathology
  • Cerebral Infarction / drug therapy*
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / pathology
  • Cyclosporins / administration & dosage*
  • Enzyme Inhibitors / administration & dosage*
  • Injections, Intraperitoneal
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology

Substances

  • Cyclosporins
  • Enzyme Inhibitors