Therapeutic approaches to vascular protection in ischemic stroke

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

Reperfusion with recombinant tissue plasminogen activator (tPA) sometimes causes catastrophic hem-orrhagic transformation (HT) in the ischemic brain. Consequently, the application of tPA has been strictly limited. Recent studies have indicated that matrix metalloproteinases (MMPs), especially MMP-9, play a critical role in blood brain barrier (BBB) disruption in the ischemic brain, leading to brain edema and HT. In the ischemic brain, free radicals and exogenous tPA itself can trigger MMP-9 activation through several signaling pathways containing LDL receptor-related protein (LRP) and proteinase-activated receptor 1 (PAR1). Therapeutic targeting of free radicals and MMP-9/t-PA related signaling pathways might be promising approaches to minimizing catastrophic HT in acute stroke patients. We provide an overview of the available scientific reports to improve our understanding of the mechanisms leading to HT, and highlight recent progress in the development of new therapeutic strategies for preventing HT in the post-stroke brain.

Original languageEnglish
Pages (from-to)219-223
Number of pages5
JournalActa medica Okayama
Volume65
Issue number4
Publication statusPublished - Aug 1 2011

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Keywords

  • Cerebral ischemia
  • Free radical
  • Hemorrhagic transformation
  • Matrix metalloproteinase-9
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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