Can the phase lag between arterial pulsations and transmantle pressure fluctuations explain glymphatic flow through periarterial spaces?*

The glymphatic system involves bulk motion of CSF through the perivascular spaces surrounding arteries and veins that penetrate the brain. In the perivenous spaces this bulk fluid motion occurs in the direction of the time-averaged transmantle pressure gradient, associated with the slight net overpressure found in the interior of the brain. However, in the periarterial spaces the bulk motion paradoxically occurs in the opposite direction. Experimental observations have shown that pulsations of the arterial wall driven by the cardiac cycle (absent in perivenous spaces) play a key role, but the precise mechanism connecting the fast, one-second, wall pulsations to the slow, time-averaged, bulk motion remains unclear. The present study employs an analytical model informed by synchronized magnetic resonance measurements to test whether the temporal interplay between the arterial pulsations and the fluctuations in transmantle pressure, which has been suggested to play a role in perivascular flow across the spinal cord (Bilston et al., J. Neurosurg. 112(4), 2010), can provide a pumping mechanism capable of driving a net periarterial flow against the existing time-averaged adverse pressure gradient.