Estimates for the astrocyte endfoot sheath permeability of the extra-cellular pathway

Abstract

BackgroundAstrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of the brain parenchyma. Detailed fluid mechanical models of diffusive and advective transport in the brain are promising tools to investigate theories of transport. MethodsWe derive theoretical estimates of astrocyte endfoot sheath permeability for advective and diffusive transport and its variation in microvascular networks from mouse brain cortex. The networks are based on recently published experimental data and generated endfoot patterns are based on Voronoi tessellations of the perivascular surface. We estimate corrections for projection errors in previously published data. ResultsWe provide structural-functional relationships between vessel radius and resistance that can be directly used in flow and transport simulations. We estimate endfoot sheath filtration coefficients in the range Lp = 0.2 x 10-10 m Pa-1 s-1 to 2.7 x 10-10 m Pa-1 s-1, diffusion membrane coefficients in the range CM = 0.5 x 103 m-1 to 6 x 103 m-1, and gap area fractions in the range 0.2 % to 0.6 %. ConclusionsThe astrocyte endfoot sheath surrounding microvessels forms a secondary barrier to extra-cellular transport, separating the extra-cellular space of the parenchyma and the perivascular space outside the endothelial layer. The filtration and membrane diffusion coefficients of the endfoot sheath are estimated to be an order of magnitude lower than the extra-cellular matrix while being two orders of magnitude higher than the vessel wall.