Central Nervous System: Microanatomy

The immune response of a tissue or organ is tightly tied to its anatomy, its cellular and acellular composition, the extent and type of vascularization, and the presence or absence of lymphatic drainage. This is particularly true of the central nervous system (CNS) which, to protect the delicate nonregenerating neurons, is designed to minimize the entry of potential antigens and cells from the blood. As such, the brain is sealed from the circulation via complex tight junctions between endothelial cells and a unique double basement membrane structure, which together constitute the blood–brain barrier (BBB). Likewise, the cerebrospinal fluid is sealed from the blood via the blood–cerebrospinal fluid barrier (BCSFB) manifested by the tight junctions between epithelial cells of the choroid plexus. The ability of the CNS to meet immunological challenges is tied to specialized microdomains that are largely associated with the BBB and the BCSFB. We describe here where these microdomains occur, their cellular and extracellular matrix composition, and their function as defined from studies of autoimmune responses in the CNS and reperfusion injury after ischemic stroke.