Choroid Plexus and the Cerebrospinal-Interstitial Fluid Systems

In most organs of the body, other than the central nervous system (CNS), extracellular fluid is derived from the blood, and drains along lymphatics to regional lymph nodes. Such a system of lymphatic drainage has a well-characterized role in B- and T-lymphocyte-mediated immune reactions (1). By contrast, extracellular fluid associated with the CNS falls into two main categories: cerebrospinal fluid (CSF) and interstitial fluid (ISF), which are, to varying degrees, separate. The relationship between the CNS and the immune system is not as well-characterized as in other organs. CSF is produced by the choroid plexus and fills the ventricular system of the brain and the craniospinal subarachnoid space. In human, CSF drains mostly into the blood, by bulk flow through arachnoid villi and granulations associated with the major venous sinuses (2); ISF drains along perivascular channels surrounding cerebral and leptomeningeal arteries, and is thus separated from CSF. Much of the CSF and the ISF in the rat drains via nasal lymphatics to regional lymph nodes, although these fluids also enter directly into the blood through primitive arachnoid villi (3,4). Although ISF drains from the human CNS along perivascular pathways that are separated from the CSF in the subarachnoid space, it is not clear how much drains to regional lymph nodes. The complex relationship between the CNS and the immune system is reflected by the “immunological privilege” of the CNS, whereby tissue allografts survive for substantially longer periods in the CNS than in other organs of the body (3).