The findings that interstitial bulk flow may be drained from the brain via lymphatic channels (ie, cervical lymph nodes) suggest that a conventional lymphatic system might exist in the mammalian brain. A number of recent studies
8-11 convincingly show the presence of a highly polarized lymphatic vessel system that facilitates the transport of interchangeable CSF and ISF out of the brain. The glymphatic system, appropriately named based on its functional similarity to the lymphatic system in the periphery,
11 acts as a brain-wide convective flux of CSF and ISF that is strictly dependent on isoform water channel aquaporin-4 (AQP4) expressed in astrocyte foot processes.
12 It is now clear that aquaporin proteins regulate the movement of water across biological membranes, including astrocytic membranes of the VRS and the BBB.
3 Thus, CSF and ISF, both solute-bearing liquids filtered from the blood, enter the VRS along penetrating arterioles, where they diffuse primarily through AQP4 channels, ultimately emptying into the jugular vein.
3,11 This glymphatic hydrodynamic process is bidirectional in terms of communication flux and is driven, in part, by respiratory and cardiac pressure pulsations.
8 These latter findings suggest that arterial pulsatility drives clearance of interstitial solutes and fluids from the brain (
Figure 1). Indeed, inspiratory thoracic pressure reduction is the major regulator of human CSF flow, as demonstrated with real-time magnetic resonance (MR) imaging at high spatial and temporal resolutions.
13