Abstract

The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells. Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus permits direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of the arachnoid granulations. The functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport. , An extra layer lines the brain The traditional view is that the brain is surrounded by three layers, the dura, arachnoid, and pia mater. Møllgård et al . found a fourth meningeal layer called the subarachnoid lymphatic-like membrane (SLYM). SLYM is immunophenotypically distinct from the other meningeal layers in the human and mouse brain and represents a tight barrier for solutes of more than 3 kilodaltons, effectively subdividing the subarachnoid space into two different compartments. SLYM is the host for a large population of myeloid cells, the number of which increases in response to inflammation and aging, so this layer represents an innate immune niche ideally positioned to surveil the cerebrospinal fluid. —SMH , A fourth meningeal layer acts as a barrier that divides the subarachnoid space into two distinct compartments.