140 ml in an adult man) per minute, or about 500 ml in 24 hours (13:24-27). Small hydrostatic pressure changes caused by such high production rates result in circulation of the CSF. This circulation results in a biochemical interchange at the CSF-brain barrier.
The CSF-brain barrier consists of the pia mater overlying the brain surface and the ependyma lining the ventricular system. It provides relatively little restriction to CSF substances entering the brain parenchyma. Small water-soluble molecules appear to pass by simple diffusion into the extracellular space. In contrast, the blood-brain barrier serves as a major physiologic boundary. In some ways, the BBB provides an interface which is equivalent to both the blood-CSF and CSF-brain barriers combined. It may be defined as "a collection of anatomic, biochemical, and transport specializations expressed by microvascular endothelial cells within the CNS (10:21)." The entire CNS possesses a rich blood supply. The BBB thus consists of a highly organized multicellular complex including these capillaries' endothelium, as well as astrocytes, pericytes, and microglia (9:87-88). Hence, this modified tight epithelium is essentially a sheet of cells on a basement membrane (4:26).
The first researcher to point out the capillary endothelium's importance to the BBB was the German pathologist, Spatz (1933). Spatz noticed that following intravenous injection of various dyes, the brain's capillaries remained unstained (5:1-40). His observations thus indicated that the BBB interface occurs at the contact surface between the blood plasma and the luminal capillary membrane. It has since been shown, however, that the effectiveness of the barrier depends primarily on interconnections which occur between the endothelial cells. In nonneural capillaries, open intercellular clefts permit the passage of water-soluble molecules. In contrast, within neural capillaries this cleft path...