Fig. 2. Meningeal and parenchymal access of immune cells.

(A) During the steady state, Tcells (and presumably other immune cells) circulate through the meningeal spaces. Their primary entry site is via the meningeal blood vessels, where the immune cells need to cross the blood-meningeal barrier (BMB) to enter the meningeal space. Blood-borne immune cells do not cross the blood-brain barrier (BBB) in a healthy situation. (B) Choroid plexus endothelial cells are fenestrated, which allows immune cells to easily cross them. For the immune cells to make their way into the CSF, however, they need to also cross a tight barrier of choroid plexus epithelial cell layer connected by tight junctions. (C and C′) Under pathological conditions such as inflammation, immune cells extravasate through the meningeal vessels and then cross the pial layer to infiltrate the brain parenchyma (C) or, more plausibly, the meningeal inflammatory environment results in the production of chemokines that, upon diffusion into the parenchyma (across pia), recruit peripheral immune cells across the BBB (C′).