The glymphatic hypothesis: the theory and the evidence

The glymphatic hypothesis proposes a mechanism for extravascular transport into and out of the brain of hydrophilic solutes unable to cross the blood-brain barrier. It suggests that there is a circulation of fluid carrying solutes inwards via periarterial routes, through the interstitium and outwards via perivenous routes. This review critically analyses the evidence surrounding the mechanisms involved in each of these stages. There is good evidence that both influx and efflux of solutes occur along periarterial routes but no evidence that the principal route of outflow is perivenous. Furthermore, periarterial inflow of fluid is unlikely to be adequate to provide the outflow that would be needed to account for…