The brain depends on other organ systems of the body for oxygen, nutrients, and the elimination of metabolic byproducts. The
primary route for such transfer of these essentials is the cerebrovasculature. The cerebrovasculature also participates in
metabolizing or excluding xenobiotics, segregating components of the immune response, regulating pH and osmolarity of the
cerebrospinal fluid, selectively distributing hormones, and impeding pathogenic invasion. Various aspects of these diverse
functions are attributed to the complex structural and molecular properties of cerebral endothelial cells collectively referred
to as the blood-brain barrier (1
–7
). The hallmark structural specialization of the blood-brain barrier is the tight junction between the endothelial cells,
which prevents diffusion of plasma proteins and molecules of a similar size or larger (8
–12
). Other structural specializations include close apposition of astrocytic endfeet, sparsely distributed pericytes, and extensive
association with microglia. Molecular specializations include endothelial expression of transporters and enzymes, such as
those involved in xenobiotic metabolism (12
–27
).