Fig. 1

Principal features of the proposed glymphatic circulation. Periarterial inflow of cerebrospinal fluid, shown on the left, enters the interstitial fluid in the parenchyma by crossing a layer of glial endfeet assisted by the presence of aquaporin 4 (AQP4) water channels in the endfoot membrane facing the perivascular space. The fluid then flows through the interstitial spaces propelling solutes towards the perivenous conduits, shown on the right, leading to outflow from the brain. Flow in the perivascular space of a blood vessel is in the same direction as the blood flow, but the orientations of arterioles and venules vary and are not strictly antiparallel. Similar portrayals of the glymphatic hypothesis with varying artistic embellishments have been published repeatedly [11, 34, 36, 38, 42, 46, 238,239,240,241]. Above and in many other published figures flow is portrayed as sweeping solutes towards the venules where they become more concentrated. It is argued in Sect. 5.4 that such a sweeping effect is unlikely to occur