Abstract
The flow of cerebrospinal fluid along perivascular spaces (PVSs) is an important part of the brain’s system for delivering nutrients and eliminating metabolic waste products (such as amyloid-β); it also offers a pathway for the delivery of therapeutic drugs to the brain parenchyma. Recent experimental results have resolved several important questions about this flow, setting the stage for advances in our understanding of its fluid dynamics. This review summarizes the new experimental evidence and provides a critical evaluation of previous fluid-dynamic models of flows in PVSs. The review also discusses some basic fluid-dynamic concepts relevant to these flows, including the combined effects of diffusion and advection in clearing solutes from the brain.
Highlights
Perivascular spaces (PVSs) in the brain are channels that surround the blood vessels and are filled with cerebrospinal fluid (CSF)
Various mechanisms have been proposed as the driving force for this flow: an overall pressure gradient created by the production of CSF in the choroid plexuses; a pressure gradient driven by respiration [9]; or a peristaltic flow driven by arterial pulsations due to the heartbeat [6,10], a mechanism appropriately named perivascular pumping by Hadaczek et al [11]
This review focuses rather narrowly on the fluid dynamics of the flow of CSF in PVSs and on the relative roles of advection and diffusion in these flows, with an emphasis on the implications of recent experimental results
Summary
Perivascular spaces (PVSs) in the brain are channels that surround the blood vessels (e.g. arteries and veins) and are filled with cerebrospinal fluid (CSF). To be discussed below, have cleared up several important questions concerning the nature of flows of CSF in PVSs, providing a much firmer basis for future modelling of these flows. Reasonable goals would be to develop a satisfactory computational model of the flow observed, in detail, in the PVSs around pial arteries in mice, and to develop a relatively simple hydraulic network model (or lumped-parameter model) of flows and diffusion in the entire glymphatic system. Progress towards these goals is reviewed here. For a broader view of the fluid dynamics of CSF and related clinical issues, see the reviews by Kurtcuoglu [17], Brinker et al [14] and Linninger et al [18]; for a more general discussion of the role of diffusion, see the review by Nicholson & Hrabětová [19]
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