Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia

Yvan Gasche, Jean Christophe Copin, Taku Sugawara, Miki Fujimura, Pak H. Chan

Research output: Contribution to journalArticle

303 Citations (Scopus)

Abstract

Oxidative stress generated during stroke is a critical event leading to blood-brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion-induced BBB disruption in mice deficient in copper/zinc-superoxide dismutase (SOD1) was reduced by 88% (P < 0.0001) and 73% (P < 0.01), respectively, after 3 and 7 hours of reperfusion occurring after 1 hour of ischemia by the inhibition of matrix metalloproteinases. Accordingly, the authors show that local metalloproteinase-generated proteolytic imbalance is more intense in ischemic regions of SOD1 mice than in wild-type litter mates. Moreover, active in situ proteolysis is, for the first time, demonstrated in ischemic leaking capillaries that produce reactive oxygen species. By showing that oxidative stress mediates BBB disruption through metalloproteinase activation in experimental ischemic stroke, this study provides a new target for future therapeutic strategies to prevent BBB disruption and potentially reperfusion-triggered intracerebral hemorrhage.

Original languageEnglish
Pages (from-to)1393-1400
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number12
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • Blood-brain barrier
  • Metalloproteinases
  • Oxidative stress
  • Stroke
  • Vasogenic edema

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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