BME Seminar: “Capillary sensing of neuronal activity and the regulation of cerebral blood flow…”

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Nikolaos Tsoukias, Ph.D.
Professor of Biomedical Engineering
Florida International University

“Capillary sensing of neuronal activity and the regulation of cerebral blood flow in health and in disease: Insights from a multiscale model of the brain vasculature”

Abstract: On demand control of local CBF is crucial for maintaining normal brain function and is compromised in brain disorders. Capillary-mediated signaling has emerged as a significant component of neurovascular coupling (NVC), allowing blood perfusion to match local demands in the brain. Capillary endothelial cells (cECs) can sense neuronal activity and initiate electrical signals to induce upstream vessel dilations. In addition, capillary pericytes (PCs) may respond to electrical, mechanical and metabolic signals to modulate tone and capillary diameter. The contribution of these mechanisms for micro and macro level control of CBF is an area of active investigation. We combine in vitro, ex vivo, and in vivo data with a first-of-its-kind multiscale model of cerebral blood flow to explore how signals in cerebral capillaries and arterioles intersect to coordinate blood flow distribution in the brain. Models of capillary endothelial cells (cECs) and PCs, and of arteriolar endothelial (ECs) and smooth muscle (SMCs) cells, capture membrane potential and Ca2+ dynamics. Cell-level models are electrically coupled to form vascular segments and integrated in realistic reconstructions of cerebral vascular networks that contain hundreds of thousands of vessel segments and millions of cells. Biomechanical models translate mural cell Ca2+ into changes in vessel diameters. Hemodynamic simulations predict pressure, flow, and red blood cell distribution in a dynamically changing vascular network that responds to chemo-mechanical stimuli. Results support cECs acting as sensors of neuronal activity. We provide evidence for electrical excitability in the cerebral endothelium that allows regenerative retrograde propagation of electrical signals towards upstream feeding vessels and robust increases in local CBF. We explore the physiological relevance of capillary constrictions and propose that contractile PCs play a critical role in myogenic autoregulation and in preserving blood supply to deeper and more vulnerable brain regions. We use the model to relate cell-level changes in disease to dysregulation of blood perfusion at the macroscale.

Bio: Dr. Nikolaos M. Tsoukias is Professor of Biomedical Engineering at Florida International University. He received his B.S. in Chemical Engineering from the National Technical University of Athens, Greece in 1994 and a doctorate in Engineering from the University of California, Irvine in 1999. Upon completion of a three-year research fellowship at Johns Hopkins University School of Medicine, he joined Florida International University in 2003. He was the 2006 recipient of the Arthur C. Guyton award for excellence in integrative physiology by the American Physiological Society. From 2015 to 2020 he joined the National Technical University of Athens, Greece as a faculty of Chemical Engineering. His research interests are in the areas of mathematical modeling, microvascular physiology and biotransport. Dr. Tsoukias is a member of the Biomedical Engineering Society, the American Heart Association, and the Microcirculatory Society. His research has been supported by the American Heart Association and the National Institutes of Health.