Mapping the Brain's Glymphatic System.

The glymphatic system is a fluid-transport framework in which cerebrospinal fluid (CSF) enters the brain along perivascular routes, exchanges with interstitial fluid (ISF), and exits toward venous, perineural, and meningeal lymphatic pathways enabling waste clearance. Recent studies have clarified the anatomical components that regulate solute movement. The perivascular astrocyte endfeet, which are enriched in polarized aquaporin-4 (AQP4) expression, create a high-permeability water interface that facilitates CSF-ISF exchange. Multiscale physical drivers such as cardiac pulsation, arteriolar vasomotion, and brain-state changes during sleep regulate the timing and efficiency of the glymphatic transport. A broad spectrum of solutes is transported through this pathway, from small metabolites to extracellular proteins including amyloid-β and tau, as well as exogenous tracers and some lipid-associated species. Glymphatic redistribution may interface with other clearance systems, including the brain-to-blood efflux via blood-brain barrier (BBB) transport, intramural periarterial drainage (IPAD) that clears along vascular basement membranes and the meningeal lymphatic pathways that drain macromolecules to deep cervical lymph nodes. These different routes may be interconnected and may represent a waste clearance network with complementary roles assigned to different mechanisms. Moreover, state dependence (notably sleep) and vascular health modulate glymphatic flux, offering plausible links between glymphatic system dysfunction, aging and neurodegeneration. Methodological advances-from intrathecal contrast magnetic resonance imaging (MRI) to