Abstract
The brain possesses an intricate network of interconnected fluid pathways that are vital to the maintenance of its homeostasis. With diffusion being the main mode of solute transport in cerebral tissue, it is not clear how bulk flow through these pathways is involved in the removal of metabolites. In this computational study, we show that networks of astrocytes may contribute to the passage of solutes between tissue and paravascular spaces (PVS) by serving as low resistance pathways to bulk water flow. The astrocyte networks are connected through aquaporin-4 (AQP4) water channels with a parallel, extracellular route carrying metabolites. Inhibition of the intracellular route by deletion of AQP4 causes a reduction of bulk flow between tissue and PVS, leading to reduced metabolite clearance into the venous PVS or, as observed in animal studies, a reduction of tracer influx from arterial PVS into the brain tissue.
Highlights
Computational methods for the study of cerebral fluid dynamics have made great strides in recent years, and have become valuable tools that can complement experimental approaches[11,12,13,14]
With the ECS and capillary basement membrane having a higher resistance to fluid flow than the intracellular space, water moves preferentially through the latter at a ratio of 3:1
We have shown how parallel extracellular and intracellular pathways established by astrocyte networks may facilitate bulk fluid flow between adjacent arterial and venous paravascular spaces
Summary
Computational methods for the study of cerebral fluid dynamics have made great strides in recent years, and have become valuable tools that can complement experimental approaches[11,12,13,14]. We aim to elucidate through numerical experiments the changes in fluid flow that lead to altered tracer distribution patterns upon AQP4 deletion observed in vivo. The underlying mathematical model considers both intra- and extracellular water pathways in a network of astrocytes between two neighbouring arterial and venous PVS. Based on the calculated fluid flow, we further comment on the relative contributions of advection and diffusion to solute transport in the extracellular and paravascular spaces
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