The blood-brain barrier (BBB) principally consists of the interface between the blood and the brain's extracellular fluid. Evidence for such a barrier was first observed over 100 years ago. As with other physiologic phenomena, the BBB's structure and function are intimately related. The different anatomic features of the barrier give rise to its selective permeability. In the normal state, this "modified tight epithelium" provides an element of control over the brain's ambient environment. Furthermore, blood-brain barrier dysfunction may be an important etiological factor in a number of neurologic diseases.
Perhaps the first scientific researcher to document the occurrence of a blood-brain barrier was Paul Ehrlich (1885, 1906) (10:1). He observed that intravenous injection of water-soluble vital dyes colored all of the body's tissues except for those of the central nervous system (CNS). The physiologic mechanisms underlying this "hindrance to diffusion," however, remained unclear for many years (5:1-40). It wasn't until the early years of this century, that Stern and Gautier (1921, 1922) studied the movement of different substances into the brain. From their observations, the two researchers concluded that the cerebrospinal fluid (CSF) acts as an intermediary between the blood and the CNS (6:28). Eventually, their work led to the identification of two separate barriers: the blood-CSF barrier and the BBB.
It is now known, however, that three separate barriers actually exist between the three fluid compartments of the brain (e.g., the cerebrospinal fluid, the extracellular fluid (ECF), and the blood). One of these interfaces, the blood-CSF barrier occurs in the choroid plexuses. These richly vascularized epithelial tissues project into the major ventricles. It is at the choroid plexus that approximately 85% of the CSF is produced. This CSF production occurs at a rate of about 0.4-0.6% of the total volume (e.g., ...