Dissociation and protection of the neurovascular unit after thrombolysis and reperfusion in ischemic rat brain

Toru Yamashita, Tatsushi Kamiya, Kentaro Deguchi, Toshiki Inaba, Hanzhe Zhang, Jingwei Shang, Kazunori Miyazaki, Aiji Ohtsuka, Yasuo Katayama, Koji Abe

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130 Citations (Scopus)

Abstract

In the ischemic brain, reperfusion with tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT); however, the mechanism remains elusive. Here, we show that the basement membrane, and not the endothelial cells, is vulnerable to ischemic/reperfusion injury with tPA treatment. We treated a spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) with vehicle alone, tPA alone, or a free radical scavenger, edaravone, plus tPA. Light and electron microscopic analyses of each microvascular component revealed that the basement membrane disintegrated and became detached from the astrocyte endfeet in tPA-treated animals that showed HT. On the other hand, edaravone prevented the dissociation of the neurovascular unit, dramatically decreased the HT, and improved the neurologic score and survival rate of the tPA-treated rats. These results suggest that the basement membrane that underlies the endothelial cells is a key structure for maintaining the integrity of the neurovascular unit, and a free-radical scavenger can be a viable agent for inhibiting tPA-induced HT.

Original languageEnglish
Pages (from-to)715-725
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number4
DOIs
Publication statusPublished - Apr 1 2009

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Keywords

  • Cerebral ischemia
  • Hemorrhagic transformation
  • Ischemia/reperfusion injury
  • Plasminogen activators
  • Thrombolysis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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