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Rho‐kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia
Author(s) -
Yagita Yoshiki,
Kitagawa Kazuo,
Sasaki Tsutomu,
Terasaki Yasukazu,
Todo Kenichi,
OmuraMatsuoka Emi,
Kaibuchi Kozo,
Hori Masatsugu
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21375
Subject(s) - fasudil , ischemia , rho associated protein kinase , medicine , rho kinase inhibitor , endothelial stem cell , microcirculation , kinase , microbiology and biotechnology , chemistry , biology , biochemistry , in vitro
Microcirculatory disturbances contribute to the expansion of infarct lesions after focal cerebral ischemia. Recently, it was shown that Rho‐kinase involves in endothelial dysfunction via down‐regulation of endothelial nitric oxide synthase function in a rodent stroke model. However, it is not clear whether endothelial Rho‐kinase is activated in vivo or Rho‐kinase activation contributes to microcirculatory disturbances after cerebral ischemia. In this study, we assessed the temporal and spatial profiles of Rho‐kianse activity and the effect of the Rho‐kinase inhibitor fasudil on microcirculatory disturbances in the focal brain ischemia. Rho‐kinase activation was evaluated by analyzing the phosphorylation of adducin, a substrate of Rho‐kinase, by immunohistochemistry. Staining for p‐adducin was found in endothelia in the ischemic area 6 hr after induction of ischemia. Microcirculatory disturbances and increased endothelial cell staining for von Willebrand factor (vWF) were observed in the same area. Postischemic treatment with fasudil suppressed endothelial Rho‐kinase activation, preserved microcirculation, and inhibited endothelial cell vWF staining. These effects resulted in inhibition of infarct expansion and improvement of neurologic deficits. These findings indicate that Rho‐kinase is activated in the endothelial cells and contributes to microcirculatory disturbances in cerebral ischemia. The vascular protective effect of Rho‐kinase inhibitors may be useful in the treatment of the acute phase of ischemic stroke. © 2007 Wiley‐Liss, Inc.