Pericyte protection by edaravone after tissue plasminogen activator treatment in rat cerebral ischemia

Kentaro Deguchi, Ning Liu, Wentao Liu, Yoshio Omote, Syoichiro Kono, Taijun Yunoki, Shoko Deguchi, Toru Yamashita, Yoshio Ikeda, Koji Abe

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Pericytes play a pivotal role in contraction, mediating inflammation and regulation of blood flow in the brain. In this study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone. Immunohistochemistry and Western blot analyses showed that the overlap between platelet-derived growth factor receptor β-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO). The number of pericytes and the overlap with NAGO decreased with tPA but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes, resulting in the detachment from astrocytes and a decrease in glial cell line-derived neurotrophic factor secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes. The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can greatly ameliorate such damage after acute cerebral ischemia in rats.

Original languageEnglish
Pages (from-to)1509-1519
Number of pages11
JournalJournal of Neuroscience Research
Volume92
Issue number11
DOIs
Publication statusPublished - 2014

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Keywords

  • Cerebral ischemia
  • Edaravone
  • Neurovascular unit
  • Pericyte
  • TPA

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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