FIGURE 17.
Plausible fluid transport routes and their dependence on the polarized expression of aquaporin 4 (AQP4) at perivascular astrocytic endfeet. Directional fluid transport from arterial to venous vasculature would require differential conditions at the site of influx (left) and efflux (right ) of fluid. Possible flow pathways can be largely divided into transcellular or paracellular transport routes. Transcellular routes (top row) would consist of direct entry of fluid through AQP4 channels, and could be subdivided into the following: 1: trans-astrocytic fluid transport, where fluid enters the astrocyte at the endfoot and continues through the soma and the greater glial syncytium following a largely intracellular pathway, or 2: trans-endfoot fluid transport, where fluid enters into the endfoot and rapidly exits into the extracellular space (ECS) without entering the soma, thus following a largely extracellular pathway interspersed with short segments of intracellular transport. Alternatively, fluid may also follow paracellular routes (bottom row), which would consist of fluid transport through the clefts formed by neighboring endfeet. This primarily extracellular transport route would rely indirectly on AQP4 water channel expression. 3: Hydrostatic pressure gradients, between the arterial and venous sides of the extracellular space could drive directional fluid flow toward the region of lower pressure (Partery > PECS > Pvein). 4: osmotic pressure gradients could be generated by astrocytic ionic fluxes (e.g., K+ spatial buffering) that in part depend on AQP4 polarization. Directional transport of extracellular osmoles could potentially drive fluid entry between endfeet toward efflux sites (σπvein > σπECS > σπartery). PVS, perivascular space.