title: The role of Rho/Rho-kinase pathway and the neuroprotective effects of fasudil in chronic cerebral ischemia.
abstract: The Rho/Rho-kinase signaling pathway plays an important role in cerebral ischemia/reperfusion injury. However, very few studies have examined in detail the changes in the Rho/Rho-kinase signaling pathway in chronic cerebral ischemia. In this study, rat models of chronic cerebral ischemia were established by permanent bilateral common carotid artery occlusion and intragastrically administered 9 mg/kg fasudil, a powerful ROCK inhibitor, for 9 weeks. Morris water maze results showed that cognitive impairment progressively worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative RT-PCR and western blot analysis showed that the expression levels of Rho-kinase, its substrate myosin-binding subunit, and its related protein alpha smooth muscle actin, significantly increased after chronic cerebral ischemia. TUNEL staining showed that chronic cerebral ischemia could lead to an increase in neuronal apoptosis, as well as the expression level of caspase-3 in the frontal cortex of rats subjected to chronic cerebral ischemia. Fasudil treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, and decreased the expression level of Rho-kinase, myosin-binding subunit and alpha smooth muscle actin. Furthermore, fasudil could regulate cerebral injury by reducing cell apoptosis and decreasing caspase-3 expression in the frontal cortex. These findings demonstrate that fasudil can protect against cognitive impairment induced by chronic cerebral ischemia via the Rho/Rho-kinase signaling pathway and anti-apoptosis mechanism.
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Yan
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Jin-Ting
authors.initials: JT
authors.lastname: He
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Mang
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Yan-Kun
authors.identifier: 0000-0002-1267-3208
authors.initials: YK
authors.lastname: Shao
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Zhong-Xin
authors.identifier: 0000-0001-7066-7159
authors.initials: ZX
authors.lastname: Xu
keywords: Rho-kinase; alpha smooth muscle actin; apoptosis; caspase-3; chronic cerebral ischemia; cognitive impairment; fasudil; myosin-binding subunit; nerve regeneration; neural regeneration