Thomas Willis Lecture: Targeting Brain Arterioles for Acute Stroke Treatment.

Cerebral infarction or ischemic death of brain tissue, most notably neurons, is a primary response to vascular occlusion that if minimized leads to better stroke outcome. However, many cell types are affected in the brain during ischemia and reperfusion, including vascular cells of the cerebral circulation. Importantly, the structure and function of all brain vascular segments are major determinants of the depth of ischemia during the occlusion, the extent of collateral flow (and therefore amount of potentially salvageable tissue) and the degree of reperfusion. Thus, appropriate function of the cerebral circulation can influence stroke outcome. The brain vasculature is also directly involved in secondary injury to ischemia, including edema, hemorrhage, and infarct expansion, and provides a key delivery route for neuroprotective agents. Therefore, the cerebral circulation provides a therapeutic target for multiple aspects of stroke injury, including aiding neuroprotection. Understanding how ischemia and reperfusion affect the brain vasculature is key to this therapeutic potential, that is, vascular protection. This report is focused on regional differences in the cerebral circulation, how ischemia and reperfusion differentially affects these segments, and how the response of large versus small vessels in the brain to ischemia and reperfusion can influence stroke outcome. Last, how chronic hypertension, a common comorbidity in patients with stroke, affects the brain microvasculature to worsen stroke outcome will be described.