Increased leukocyte ROCK activity in patients after acute ischemic stroke

Steven K. Feske, Farzaneh A. Sorond, Galen V. Henderson, Minoru Seto, Asako Hitomi, Koh Kawasaki, Yasuo Sasaki, Toshio Asano, James K. Liao

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Background: Rho-kinase (ROCK) is a downstream effector of Rho GTPase that is known to regulate various pathological processes important to the development of ischemic stroke, such as thrombus formation, inflammation, and vasospasm. Inhibition of ROCK leads to decreased infarct size in animal models of ischemic stroke. This study tests the hypothesis that ROCK activity increases during the acute phase of ischemic stroke. Methods: Serial blood samples were drawn from 10 patients with acute ischemic stroke presenting within 24 h of symptomonset and with NIHSS scores ≥4. Sampleswere taken at 24, 48, and 72 h. Leukocyte ROCK activity was determined by immunoblotting leukocyte lysates with antibodies to the phosphorylated formofmyosin-binding subunit (P-MBS) ofmyosin light chain phosphatase (MLCP).MBS and P-MBS contents were normalized to α-tubulin, and ROCK activity was expressed as the ratio of P-MBS to MBS. ROCK activities in these 10 patients were compared to baseline ROCK activities in 10 control subjectswithout acute illness andmatched for sex, age, and number of vascular risk factors using a two-tailed Student's t-test. Results: The mean NIHSS score in patients with stroke was 15.4. ROCK activity was significantly increased at 24 and 48 h in patients after acute ischemic stroke when compared to control values, with peak elevations at 48 h after stroke onset. There was no apparent correlation between ROCK activity and stroke severity based on NIHSS. Conclusions: Leukocyte ROCK activity is increased in patients after acute ischemic stroke with maximal activity occurring about 48 h after stroke onset. These findings suggest that activation of ROCK may play a role in the pathogenesis of ischemic stroke in humans.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalBrain research
Volume1257
DOIs
StatePublished - Feb 2009

Keywords

  • Acute ischemic stroke
  • Fasudil
  • ROCK
  • Rho-kinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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