FIGURE 1.

Glymphatic system, neurovascular unit (NVU), and the blood–brain-barrier. The glymphatic system contributes to the transport of nutrients and signaling molecules into the brain parenchyma meanwhile promoting the clearance of proteins and interstitial waste solutes out of the brain. Subarachnoid CSF enters the brain parenchyma via para-arterial spaces and then mixes with the interstitial fluid (ISF) and waste solutes in the parenchyma. Whether this occurs through convective bulk flow or diffusion remains debated. The resulting CSF-ISF fluid exchange and the interstitial waste solutes enter the paravenous space through gaps between the astrocytic end-feet to be drained either back to the CSF-dural sinus-meningeal lymphatic vessels, or to the deep cervical lymph nodes. Green arrows and shades indicate the CSF and CSF-ISF fluid transport, while black stars indicate the interstitial waste solutes that exit the parenchyma via the paravenous efflux pathway. The insert depicts the main components of the NVU at the level of intraparenchymal capillaries, including perivascular astrocytes with their end-feet, neurons, microglia, pericytes, endothelial cells (ECs), and basement membrane (basal lamina). Capillary ECs are held together by tight junctions forming the blood–brain barrier (BBB), where the different transport routes are represented, including transcellular lipophilic transport, carrier protein-mediated transport, paracellular aqueous transport, receptor-mediated transcytosis, as well as adsorptive and cell-mediated transcytosis.