Targeting cerebrovascular Rho-kinase in stroke

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.