Abstract 219: Activity-Dependent Capillary Hyperemia in The Brain Is Not Regulated by Pericytes

Activity-dependent increases in blood flow comprise the basis for functional brain imaging and are considered a hallmark of normal brain function. The central dogma of blood flow regulation states that flow changes effected by arteriolar tone drive functional hyperemia and that the capillary bed is a passive conduit for hyperemia resulting from upstream vasodilation. Recent evidence has begun to challenge this convention in cerebral blood flow control and suggests that pericytes may dilate capillaries during functional hyperemia, but whether pericytes can regulate flow of individual red blood cells (RBCs) through capillaries during sensory stimulation is unknown. Using high-speed two-photon microscopy in a live mouse model, we document that increases in RBC flow velocity and RBC flux through capillaries were detected within 1.0 second after sensory stimulation, and that the observed activity-evoked capillary hyperemia did not depend on the presence of a pericyte. We further report that local application of vasorelaxants shown to relax pericytes ex vivo did not alter resting RBC velocity in capillaries in vivo and did not affect sensory stimulation-evoked capillary RBC velocity increases. These findings support the hypothesis that cerebral capillary hyperemia occurs rapidly after sensory input, but fail to provide evidence for dynamic pericyte-dependent regulation of capillary functional hyperemia during brain activation. These results provide novel insight into the fundamental mechanisms underlying brain capillary blood flow regulation and have significant implications for targeting the disruption of cerebral microvascular blood flow characteristic of ischemic and hemorrhagic strokes.