@misc{17534, author = {Marius Causemann and Rune Enger and Marie Rognes}, title = {Computational Modeling of Astrocyte Endfeet: Insights into their Mechanical Buffering Function}, abstract = {Astrocyte endfeet encompass cerebral blood vessels, forming a nearly complete sheet, yet their functional significance remains incompletely understood. Current hypotheses include the facilitation of solute clearance [1] and regulation of arteriole vasodilation and vasoconstriction [2]. Furthermore, the abundance of Aquaporin-4 (AQP4) water channels on the endfoot side facing blood vessels raises questions about their physiological function. Recent imaging studies have demonstrated significant endfoot deformations during pronounced vasomotion during sleep [3], suggesting a potential mechanical buffering function that mitigates the mechanical forces exerted on surrounding brain tissue. In this study, we employ a biomechanical modeling approach, utilizing a geometrically- explicit representation of astrocyte endfeet, interstitial and perivascular spaces, to compute fluid flow and cell deformation in response to vasodilation and constriction. Our model characterizes the intracellular and extracellular domains as porous media separated by a permeable membrane, enabling the prediction of time-evolving extracellular and intracellular fluid flow, hydrodynamic pressure, mechanical stress, and displacement. By applying this model, we examine the impact of vasomotion and perivascular flow on the mechanics of the surrounding tissue and quantitatively compare the hydrodynamical and mechanical effects of varying AQP4 density on astrocyte endfeet. Through our comprehensive model, we aim to gain insights into the physiological role of endfeet and the involvement of AQP4 water channels, with particular emphasis on their potential mechanical buffering function during vasomotion. **References** 1. Abbott, N. Joan, et al. "The role of brain barriers in fluid movement in the CNS: is there a {\textquoteleft}glymphatic{\textquoteright}system?." Acta neuropathologica 135 (2018): 387-407., 10.1007/s00401-018-1812-4 2. Haidey, Jordan N., et al. "Astrocytes regulate ultra-slow arteriole oscillations via stretch-mediated TRPV4-COX-1 feedback." Cell reports 36.5 (2021)., 10.1016/j.celrep.2021.109405 3. Bojarskaite, Laura, et al. "Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport." Nature communications 14.1 (2023): 953., 10.1038/s41467-023-36643-5}, year = {2023}, journal = {-}, }