Rho-associated protein kinase (ROCK) is a major regulator of actin cytoskeletal organization and controls numerous cell functions in vascular smooth muscle, endothelial cells, neurons, glia, and inflammatory and blood cells. Cerebral ischemia acutely increases ROCK activity in neurons, astrocytes, and infiltrating leukocytes and ROCK inhibition has been shown to be protective in animal models of cerebral ischemia. Through multiple converging and synergistic mechanisms, ROCK inhibition increases collateral flow to extend the therapeutic window of efficacy of reperfusion therapies and prevents microvascular plugging and no-reflow to facilitate reperfusion.

Fasudil is a potent and selective ROCK inhibitor that is already employed as the clinical standard of care for two decades in acute SAH in China and Japan, where Fasudil has been safe and well tolerated. In addition, numerous safety and efficacy trials of systemic Fasudil treatment in the US and abroad have not revealed serious adverse events either with acute single doses or chronic daily dosing. Fasudil has been widely studied in preclinical trials and demonstrated efficacy in multiple species and models of stroke, in both sexes, in aged animals and comorbidities (diabetes, hyperlipidemia), with a therapeutic window of 3-6h. Moreover, Fasudil is safe in permanent ischemia, and in combination with tPA, anti-thrombotics, and statins. Since Fasudil directly and selectively inhibits ROCK activity, it rapidly and efficiently achieves the pleiotropic effects of statins and may be superior to statins in acute stroke. An abundance of evidence point to Fasudil being a promising therapeutic candidate for further study.