Stroke, especially ischemic stroke, is the second leading cause of death in people over the age of 60 and most survivors are likely to suffer varying degrees of disability for the rest of their lives. Currently, thrombolysis therapy is the only option for ischemic stroke but very few are eligible for treatment due to a narrow therapeutic window. New therapies for stroke are desperately needed. It has been shown that energy deficiency, glutamate excitotoxicity and reactive astrogliosis are three major causes of neural damage and neuronal death. Glycogen in astrocytes is the primary endogenous source of alternative cellular energy for neural cells, but studies in our laboratory have shown that glycogen breakdown is dys-regulated during ischemic stroke. Subsequent energy failure results in reduced glutamate re-uptake from the synaptic cleft potentiating excitotoxicity. These effects are all mediated by changes in astrocyte function. The Rho-kinase (ROCK) inhibitor, Fasudil, has recently been shown to reduce astrocyte reactivity and restore glutamate re-uptake in cultured cells (REF) by competing with the ATP binding site of a small GTPase, Rho protein, which is the upstream activator of ROCK. Current experiments in our laboratory have now shown that delayed treatment with Fasudil after stroke reduces over-activation of astrocytes and prevents glial scar formation by 28 days. This project will assess the effects of Fasudil on immediate responses to stroke using the endothelin-1 model of middle cerebral artery vasoconstriction in conscious rats. Fasudil or saline will commence 1 hour after stroke onset, and the brain tissue will be harvested after 24 hours to assess glycogen breakdown, and the regulation of glutamate transporter using dimethyl-labelling mass spectrometry, western-blot and immunohistochemical techniques. We hope that these studies will uncover a new treatment approach for rescuing neurons after stroke, specifically by targeting the role of astrocytes in maintaining trophic support.