Fig. 4. CNS drainage: New concepts for old.

(A) Before the discovery of meningeal lymphatic vessels, the old concept of CNS drainage was based on the fact that water from CSF is drained through arachnoid granulations, whereas macromolecules and immune cells from the CNS and the CSF are drained through the cribriform plate into nasal lymphatics and, from there, to CNS-draining deep cervical lymph nodes. (B) Discovery of the meningeal lymphatic vessels led to the hypothesis that they may drain meningeal immune cells and macromolecules from the parenchyma and the CSF, whereas the contribution of the cribriform plate as a drainage route for immune cells under homeostatic conditions needs to be reassessed. This route may be more active during neuroinflammatory conditions. Additional studies are needed to better characterize the contribution of each route of drainage for immune cells and macromolecules from the CNS and the CSF under homeostatic and pathological conditions.