Grant: Project Grant

Restoring blood flow to ischemic brain improves outcomes in patients with stroke. Although treatment with endovascular therapy (EVT) is very effective at recanalizing large cerebral vessels, over half of treated patients still have persistent major disability. Small vessels that maintain flow before and after EVT may become impaired, preventing delivery of oxygen and glucose to brain tissue. This proposal will assess the role of white blood cells in EVT treated stroke patients in contributing to poor stroke outcome. Patterns of gene expression in white blood cells from stroke patients with poor outcome even after successful EVT will be identified. We will use mouse models of stroke to study the effects of white blood cells on blood flow during and after flow in the occluded vessel is restored. Live animal imaging will permit evaluation of white blood cell activation and adhesion in relationship to blood flow cerebral microvessels and define the role of these cells in impeding flow in these vessels. Tools to deplete these cells and to genetically target activation of these cells will be used to confirm the mechanism that leads to blocked blood vessels. Strategies to modulate signalling in these cells to improve flow in microvessels and improve outcome will be examined. We aim to demonstrate how these cells are altered by stroke and contribute to microvascular failure that leads to poor outcome after stroke, and how their signalling can be targeted to improve stroke outcome.