Abstract
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 μm/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 μm/s), though reaching up to 7 μm/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 μm/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.
Highlights
The glymphatic theory [1] 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
Convective flow through the interstitium has been challenged [10, 11], even small convective flows may be important for large molecules [12] such as Amyloid-beta and tau
We find that all forces combined may induce PVS flow comparable to experimental observations [2], but that the magnitude of the static pressure gradient required for net flow suggests that its origin is still unclear
Summary
The glymphatic theory [1] 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. Many experimental findings [2,3,4,5,6,7,8] demonstrate and support that transport is faster than diffusion, while others do not [9]. The glymphatic concept involves an influx of CSF in periarterial spaces, convective flow through the interstitium and efflux in perivenous spaces. Convective flow through the interstitium has been challenged [10, 11], even small convective flows may be important for large molecules [12] such as Amyloid-beta and tau. The venous efflux is not without controversy.
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