Fig. 2

Structural and cellular compositions of the cerebral small vessels. Leptomeningeal arteries penetrate the pia mater and glia limitans from the subarachnoid space into the parenchyma, ramifying into arterioles and capillaries. In leptomeningeal arteries, endothelial cells make up a single luminal layer which are covered by multiple smooth muscle cell layers. In penetrating arterioles, endothelial cells and smooth muscle cells are single layers. In capillaries, endothelial cells form the blood–brain barrier (BBB) with pericytes and basement membrane, surrounded by astrocytic end-feet. The capillaries connect to venules flowing back into veins. In contrast to arterial smooth muscle cells, venous smooth muscle cells have flattened cell bodies and multiple processes, not fully sheathing the venules and veins. Perivascular fibroblasts and macrophages are mainly localized on arterioles and venules. Subarachnoid cerebrospinal fluid (CSF) distributes into the brain parenchyma through para-arterial spaces referred as glymphatic periarterial CSF influx. Interstitial fluid (ISF) as well as CSF diffuse into the perivenous space by bulk flow, and finally efflux into the CSF-dural sinus or cervical lymph nodes. In addition, the ISF and CSF in brain parenchyma can also enter the periarterial space from the capillary level and flow countercurrent to blood flow along arterial vessels, referred as intramural periarterial drainage (IPAD) pathway