In this paper, we adopt the term perivascular space and consider flow along arteries on the pial surface (surface arteries). The distinction is important in light of the controversy mentioned above. Initially, the term paravascular spaces was used for a Virchow-Robin type space, distinct from the perivascular intramural spaces. In conclusion, cerebral fluid flow and transport is still controversial, and the many aspects of the glymphatic hypothesis are still debated almost a decade after its inception. In particular, accumulation of amyloid in the walls of cerebral arteries has been seen in cerebral amyloid angiopathy. According to the IPAD hypothesis, fluid is drained out from the brain along the basement membranes of capillaries and arterioles. The presence and direction of flow in PVS around arteries is also debated. Tracers in the SAS have been reported to reach the ventricles without a presence in perivenous spaces. The venous efflux is also not without controversy. Convective flow through the interstitium has been challenged, although even small convective flows may be important for large molecules such as Amyloid-beta and tau. The glymphatic concept involves an influx of CSF in periarterial spaces, convective flow through the interstitium and finally efflux in perivenous spaces. Many experimental findings demonstrate and support that transport is faster than diffusion, while others do not. The glymphatic theory suggests that the interaction of cerebrospinal fluid (CSF) and interstitial fluid facilitates the brain’s clearance of metabolites via perivascular spaces (PVS) in a process faster than diffusion alone. The static CSF pressure gradient required for net flow is small, suggesting that its origin is yet to be determined. 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. Moreover, rigid motions of the artery added to the complexity of flow patterns in the PVS.
In realistic geometries, a static systemic pressure increase of physiologically plausible magnitude was sufficient to induce net flow velocities of 20–30 μm/s. In the absence of a static pressure gradient, predicted net flow velocities were small (<0.5 μm/s), though reaching up to 7 μm/s for non-physiological PVS lengths. The arterial wall expansion generated velocity amplitudes of 60–260 μm/s, which is in the upper range of previously observed values. 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 oscillatory particle movement has a clear cardiac component, while the mechanisms involved in net movement remain disputed. Experimental studies have demonstrated both net and oscillatory movement of microspheres in PVS (Mestre et al. Flow of cerebrospinal fluid (CSF) in perivascular spaces (PVS) is one of the key concepts involved in theories concerning clearance from the brain.
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