The mechanisms behind perivascular fluid flow

Flow of cerebrospinal fluid (CSF) in perivascular spaces (PVS) is one of the key concepts involved in theories concerning clearance from the brain. Experimental studies have demonstrated both net and oscillatory movement of microspheres in PVS (Mestre et al. (2018), Bedussi et al. (2018)). The oscillatory particle movement has a clear cardiac component, while the mechanisms involved in net movement remain disputed. Using computational fluid dynamics, we computed the CSF velocity and pressure in a PVS surrounding a cerebral artery subject to different forces, representing arterial wall expansion, systemic CSF pressure changes and rigid motions of the artery. The arterial wall expansion generated velocity amplitudes of 60–260 µ m/s, which is in the upper range of previously observed values. In the absence of a static pressure gradient, predicted net flow velocities were small (<0.5 µ m/s), though reaching up to 7 µ m/s for non-physiological PVS lengths. In realistic geometries, a static systemic pressure increase of physiologically plausible magnitude was sufficient to induce net flow velocities of 20–30 µ m/s. Moreover, rigid motions of the artery added to the complexity of flow patterns in the PVS. Our study demonstrates that the combination of arterial wall expansion, rigid motions and a static CSF pressure gradient generates net and oscillatory PVS flow, quantitatively comparable with experimental findings. The static CSF pressure gradient required for net flow is small, suggesting that its origin is yet to be determined. Significance Statement Cerebrospinal fluid flow along perivascular spaces is hypothesized to be instrumental for clearance of metabolic waste from the brain, such as e.g. clearance of amyloid-beta, a protein known to accumulate as plaque within the brain in Alzheimer’s patients. Arterial pulsations have been proposed as the main driving mechanism for perivascular fluid flow, but it is unclear whether this mechanism alone is sufficient. Our results show that arterial pulsations drive oscillatory movement in perivascular spaces, but also indicate that a pressure gradient is required for net flow. However, the required pressure gradient is relatively small, thus suggesting that its origins can be associated with physiological processes within the brain and/or experimental procedures.