Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Cortical spreading depression (CSD) is a slowly propagating wave of brain cell depolarization that occurs in neurological disorders such as migraine, stroke, and traumatic brain injury. Experimental and clinical evidence suggest that blood flow in the brain is decreased following CSD, and may contribute to the pathologies associated with CSD. However, the mechanisms underlying blood flow changes after CSD are unclear. Preliminary data show that the level of 20-HETE, a molecule that causes blood vessels to constrict, increases after CSD. Therefore we hypothesize that changes in 20-HETE levels may contribute to changes in blood flow following CSD. The aim of this study is to further characterize 20-HETE production and its pathophysiological role in CSD, using a combination of pharmacological, biochemical, and imaging techniques in both brain slices and intact preparations. We will chemically induce CSD in the brain, and monitor changes in blood vessel diameter and blood flow as 20-HETE levels are manipulated. The proposed study is anticipated to improve our understanding of the mechanisms involved in pathological changes in brain blood flow after CSD, facilitating the development of therapeutic approaches for various neurological conditions.