Figure 2. Glymphatic and lymphatic drainage pathways from the CNS to the cervical lymph nodes.

(A) Schematic illustration of the meningeal lymphatic vessel system in mouse cranium. The dural lymphatic vessels align with dural blood vessels and cranial nerves and exit the cranium via the foramina together with the venous sinuses, arteries, and cranial nerves. Some lymphatic vessels are also found traversing the cribriform plate with the olfactory nerves. Tracers injected into either brain parenchyma or SAS drain via the dural lymphatic vessels into dcLNs located next to the jugular vein. (B) Close-up view of ISF and CSF circulation. The perivascular glymphatic drainage system transports CSF and solutes into the brain via a periarterial pathway, whereas ISF and solutes exit the brain via the perivenous glymphatic pathway. CSF can enter the venous system via arachnoid granulations, and CSF macromolecules and immune cells are transported mainly along the dural lymphatic vessels into the lymph nodes and extracranial systemic circulation. (C) Out-of-CNS drainage routes for antigens and antigen-presenting cells (APCs). Antigens and APCs are proposed to leave the CNS via either (i) lymphatics of the cribriform plate, reaching the nasal mucosa lymphatic vasculature (particularly, dendritic cells may migrate along the rostral migratory stream [RMS] to enter the lymphatics via the olfactory bulb’s SAS); or (ii) the glymphatic pathway (as demonstrated for antigens), reaching the SAS and entering the meningeal lymphatic vasculature via SAS and trafficking to the dcLNs. APCs within the meningeal spaces may also leave through meningeal lymphatic vessels into the dcLNs. Each pathway’s contribution to cell and antigen drainage has yet to be determined.