Title: The Emerging roles of Erythrocytes in the Regulation of Cerebral Microcirculation
Abstract: Thinking, reading, writing, or throwing a baseball are all activities in which neural activity is coupled with local elevation in cerebral blood flow. The mechanisms by which neural activity triggers hyperemia have been extensively studied, in part, because neurovascular coupling forms the basis for functional brain imaging. Defects in neurovascular coupling are also believed to contribute to cognitive decline in neurodegenerative conditions such as Alzheimer disease, as well as in hypertension and stroke. Despite the uncontested tight linkage between neural activity and cerebrovascular responses, the question of what drives functional hyperemia is still debated. Most recently, it has emerged that functional hyperemia is initiated in the smallest blood vessels in brain, capillaries: activity-driven decreases in oxygen tension (PO 2 ) can directly increase the velocity of red blood cells (RBCs) passage through capillaries, measured both in vivo and ex vivo. Analysis in microfluidic chambers, in which RBC velocity can be studied in the absence of the neurovascular unit, shows that changes in PO 2 can directly trigger an increase in RBC flow velocity by increasing RBC deformability, thus decreasing vascular resistance. As such, RBCs are active players in capillary hyperemia, and promptly increase O 2 delivery in response to activity-induced localchanges in PO 2. This provides a simple yet robust mechanism for swift and precise local increases in capillary flow in response to the ever-changing patterns of neural activity within the central nervous system.
This talk describes the efforts our group has made to understand the mechanosensing dynamics of RBCs and focuses on the current findings of RBCs in the regulation of cerebral capillary hyperemia. Specifically, I will introduce a multifaceted approach we developed to dissect the molecular pathways driving the initial events leading to increased capillary RBC velocity and the engineering principles behind the change of capillary RBC velocity. Our study represents an entirely novel approach to resolve the connection between neural activity and the hemodynamic response and thus is expected to provide novel insights to neurovascular coupling and functional brain imaging and potential therapeutic targets for neurodegenerative diseases, stroke, and aging.
Biography: Jiandi Wan currently holds an assistant professor position in the Chemical Engineering Department at UC Davis and an adjunct assistant professor position at the Center for Translational Neuromedicine at University of Rochester Medical Center. He obtained bachelor and master degrees from Wuhan University and PhD from Boston University, and did postdoc trainings at Harvard University and Princeton University. Dr. Wan’s current research interests include neurovascular coupling, organ-on-chip and advanced functional materials.