Figure 1.

Updated schematic description of the glymphatic system (2022)

The glymphatic system supports the perivascular exchange of CSF and interstitial solutes throughout the CNS. This process occurs over macroscopic anatomical scales, within the perivascular influx of subarachnoid CSF into brain tissue organized along the scaffold of the arterial vascular network, and the efflux of interstitial solutes occurring toward cisternal CSF compartments associated with dural sinuses.

(A) CSF influx into brain tissue occurs along perivascular pathway surrounding penetrating arteries (A1) and is driven in part by arterial pulsation (A2). Perivascular bulk flow and interstitial solute clearance are dependent upon the astroglial water channel AQP4 localized to perivascular astroglial endfeet surrounding the cerebral vasculature (A3).

(B) Interstitial solute movement occurs through the combined effects of diffusion and advection. Advection is most rapid along privileged anatomical pathways, including intraparenchymal perivascular spaces (B1) and white matter tracts (B3), and supports the movement of large molecular weight solutes. Diffusion dominates the movement of small molecules, particularly within the wider interstitium (B2).

(C) Interstitial solutes drain from the parenchyma along white matter tracts and draining veins towards sinus-associated cisternal CSF compartments (C1). CSF solutes are cleared from the cranium via uptake into meningeal lymphatic vessels, by efflux through dural arachnoid granulations, or through clearance along cranial or spinal nerve sheathes (C2).