Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Stroke is a leading cause of death and disability in Canada, with over 100,000 strokes occurring each year. While current interventions can successfully reopen larger blocked arteries, one in three patients still fails to regain full blood flow in the smallest brain vessels, known as capillaries. This "no-reflow" phenomenon is strongly linked to poor clinical outcomes and long-term disability. Research shows that no-reflow is partly caused by "capillary stalls," where blood cells get stuck and temporarily block individual capillaries. Because capillaries are the main site of oxygen delivery, even brief stalls can negatively impact brain function. This research focuses on the capillary endothelium, the thin layer of cells lining every vessel, which uses calcium signals to regulate vessel tone and blood cell interactions. We propose that these calcium signals act as a natural mechanism to clear stalls. To test this, we will use two-photon microscopy in live mice genetically engineered to make calcium signals in their blood vessels visible. We will observe how calcium activity relates to the start, persistence, and clearance of stalls under normal conditions and after stroke. We will then manipulate calcium activity using genetic tools that either increase or decrease calcium signals, and measure the resulting effects on capillary blood flow, vessel dilation, and stall clearance. In addition, we will use complementary methods to measure regional blood flow and behavioural tests to determine if altering calcium activity improves recovery after stroke. This research highlights the overlooked role of capillaries in stroke and investigates calcium signals as a natural regulator of blood flow. By uncovering how endothelial calcium signals regulate capillary blood flow, this project could identify safer and more effective ways to restore circulation after stroke and improve quality of life for the many Canadians living with the effects of stroke.