Grant: Project Grant

Stroke is a major cause of infirmity and death worldwide, and more than 400,000 Canadians are living with the disabling consequences of stroke. It is estimated that during the next 20 years the incidence of stroke will rise by ~80%. International efforts are moving toward the goals of better preventing and curing stroke, but clinical trial have failed, leaving clot busting drugs (recombinant tissue plasminogen activator, "rtPA") and endovascular surgery as only options. However, rtPA produces detrimental side effects, limiting its use to ~10% of stroke victims. Since the consequences of stroke create a huge emotional and financial burden on patients, families, caregivers and on society, there is an urgent need to develop new drugs that could be safely administered after stroke, even beyond to critical opportunity window, to limit the disabling consequences of brain ischemia by reactivate brain plasticity. Emergency treatment for stroke aims at rapidly restoring blood flow in the affected brain region to provide nutrients and oxygen. Clot-busting drugs have thus been widely used as a first line of treatment. However, this treatment works only if given within a few hours of stroke and with safety concerns. Hence, there is an urgent need to develop new drugs to treat stroke patients in whom tPA administration was not possible, and for those with long-lasting disabilities. The objective of our project is to better understand the role of a protein (HMGB1) produced by astrocytes (glial cells of the brain) in neurovascular repair post-stroke using mice. We also aim at testing whether modulating HMGB1 function may control the demise of brain blood vessels and neurons following stroke to limit secondary injuries and/or trigger repair. We assembled a team of international experts combining relevant knowledge in vascular biology, neuroscience and stroke recovery. If successful, this novel approach could be transformative, by improving or accelerating functional recovery.