The innovative experiments of Paul Ehrlich (1) more than a century ago were the first to demonstrate that the permeability properties of cerebral vessels were different from those of non-neural vessels. He injected the aniline dye coerulean-S intravenously into rats and found that all body organs turned blue but the brain did not. These findings were later confirmed by Bouffard (2) and Goldmann (3) using intravenously injected trypan blue. These early studies led to the recognition of a barrier between blood and brain, which was not passable by trypan blue and which also led to the hypothesis at that time that the barrier was at the endothelium of intracerebral vessels (4). Although the term “blood-brain barrier” (BBB) was introduced to describe the absolute restriction of penetration of certain molecules into the brain, it now includes a variety of mechanisms, which maintain cerebral homeostasis.