Figure 2.

Detailed information on glymphatic system and IPAD pathway.

CSF from subarachnoid space flows along the periarterial space, then enters the brain parenchyma via AQP4, which is highly-expressed on the perivascular astrocytic endfeet. In the brain, the neurons and other neurocytes produce metabolic waste (Aβ, for example), which is excreted into the ISF and is mixed with CSF to achieve the ISF renewal. The mixed fluid enters the perivenous space via AQP4, then flows into the dural sinus via arachnoid granulations and the peripheral lymphatic system through the perineural space and meningeal lymphatic vessels. ISF can also enter the basement membrane of capillaries and the basement membrane surrounding SMCs of the arteries, which flows out of the brain triggered by vasomotion of arteries. AQP4: Aquaporin-4; Aβ: amyloid β; CSF: cerebrospinal fluid; IPAD: intramural periarterial drainage; ISF: interstitial fluid; SMC: smooth muscle cell.