Multiscale modeling of electromechanical coupling and hemodynamics in the cerebral microcirculation: Role of capillary pericytes in blood flow regulation

The regulation of cerebral blood flow (CBF) involves a complex interplay of signaling processes spanning various spatial and temporal scales. On demand control of local CBF is crucial for maintaining normal brain function and is compromised in brain disorders such as Alzheimer’s disease, stroke, and small vessel disease of the brain. Capillary-mediated signaling has emerged as a significant component of neurovascular coupling (NVC), allowing blood perfusion to match local demands in the brain. Capillary Pericytes (PCs) can actively regulate capillary tone and diameter and respond to electrical, mechanical or metabolic signals. In this study, we present an integrated modeling approach that can link macroscale flow responses to cell-level dynamics, and we explore the role of capillary PCs in coordinating local blood flow distribution. Models of capillary endothelial cells (cECs) and PCs, and of arteriolar endothelial (ECs) and smooth muscle (SMCs) cells, capture membrane potential and Ca 2+ 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 of arterioles and capillaries translate mural cell Ca 2+ into changes in vessel diameters. In the dynamically changing vascular network, hemodynamic simulations predict pressure, flow, and hematocrit distributions. Simulations explore the physiological relevance of capillary constrictions and propose that contractile PCs play a critical role in brain perfusion by: a) contributing to myogenic autoregulation; b) mediating the propagation of electrical signals along the microvascular network and c) regulating the distribution of blood between brain tissue layers and preserving blood supply to deeper and more vulnerable brain regions. Supported by the National Institute of Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS119971. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.