Grant: Project Grant

Cerebral Small Vessel Disease (CSVD) is estimated to cause 25% of all stroke and arises from defects in the small vessels of the brain (arterioles, capillaries and venules). Each year, ~16,000 Canadians die from stroke, of which ~4000 have CSVD. CSVD doubles the risk of a future ischemic stroke and therefore understanding its pathogenesis is urgent. However, we are limited in understanding the CSVD mechanism by the lack of technology to image small vessels in the human brain. It is only once damage reaches a threshold that MRI imaging detects the lacunar infarcts and white matter defects characteristic of CSVD, but this is relatively late in the disease progression. Long-term morbidity is high and we lack specific treatments. CSVD is suspected to have a strong genetic component, although causative genes have been elusive in the general population. My lab develops animal models of vascular stabilization and has joined forces with an international team that has identified genetic risk factors for CSVD in humans. In this proposal I exploit animal models and human genetics collaborations to identify mechanisms by which mutations in a novel CSVD genetic risk factor, Foxf2, increases CSVD risk.