Targeting cerebrovascular Rho-kinase in stroke

被引：13

作者：

Shin, Hwa Kyoung ^{[2
]}

Salomone, Salvatore ^{[3
]}

Ayata, Cenk ^{[1
]}

机构：

[1] Harvard Univ, Stroke Serv & Neurosci Intens Care Unit, Stroke & Neurovasc Regulat Lab,Dept Neurol, Massachusetts Gen Hosp,Med Sch,Dept Radiol, Charlestown, MA 02129 USA

[2] Pusan Natl Univ, Med Res Ctr Ischem Tissue Regenerat, Pusan 602739, South Korea

[3] Univ Catania, Dept Pharmacol, I-95125 Catania, Italy

来源：

EXPERT OPINION ON THERAPEUTIC TARGETS | 2008年 / 12卷 / 12期

关键词：

cerebral ischemia; fasudil; rho; rho-associated kinase; stroke;

D O I：

10.1517/14728220802539244

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: Rho and Rho-associated kinase (ROCK) play pivotal roles in pathogenesis of vascular diseases including stroke. ROCK is expressed in all cell types relevant to stroke, and regulates a range of physiological processes. Objective: To provide an overview of ROCK as an experimental therapeutic target in cerebral ischemia, and the translational opportunities and obstacles in the prophylaxis and treatment of stroke. Methods: Relevant literature was reviewed. Results: ROCK activity is upregulated in chronic vascular risk factors such as diabetes, hyperlipidemia and hypertension, and more acutely by cerebral ischemia. ROCK activation is predicted to increase the risk of cerebral ischemia, and worsen the ischemic tissue outcome and functional recovery. Evidence suggests that ROCK inhibition is protective in models of cerebral ischemia. The benefit is mediated through multiple mechanisms. Conclusion: ROCK is a promising therapeutic target in all stages of stroke.

引用

页码：1547 / 1564

页数：18

共 197 条

[21] Evidence that Rho-kinase activity contributes to cerebral vascular tone in vivo and is enhanced during chronic hypertension - Comparison with protein kinase C [J].