Grant: CIHR Fellowship

Stroke is the third leading cause of death in Canada and more than 300,000 Canadians currently live with the debilitating effects of a stroke. Characterized by a transient lack of oxygen to the brain, its detrimental effects on the brain cells last far longer than the period of anoxia, largely because of the neuroinflammation reaction that persists. Microglia, the brain's immune cells, are known to be responsible for sensing the brain environment, however, little is known about their rapid response to decreased levels of oxygen. Preliminary experiments demonstrate that the highly branched cells react within minutes to the lack of oxygen by retracting their main processes and extending smaller, actin-dependent filopodia. Because microglia use their major processes to probe the environment, this shape change is accompanied by a significant change in their sensing function. Part of my project aims at characterizing this novel functional phenotype in order to better understand what role microglia play during periods of stroke, and how this affects the long term function of the immune cells. I will also investigate which signaling pathway is responsible for this change, in the hopes of finding molecular targets for therapeutic stroke treatments. Furthermore, the multiphoton imaging technique I am using enables me to directly observe the movements of fine protrusions located on the microglia, called filopodia. These structures, known to exist on multiple cell types, have never been examined in details on microglia. We believe they are critical to the sensing function of these highly motile cells. I will examine the role of these filopodia in physiological and pathological conditions, giving us a better comprehension of how microglia move and interact with their surroundings to perform their probing functions. Understanding how microglia react during stroke and how they interact with their environment will help developing effective treatments for this disease.