Ehrlich showed in the mid-nineteenth century that when acidic dyes such as trypan blue were injected into the bloodstream most of the tissues of the body were stained, except for the brain.

The blood-brain barrier is essentially the restraint imposed upon the passage of substances from the blood into the brain or vice versa. The permeability of the blood-brain barrier and the rate at which substances pass across it is determined by the nature of the barrier and by the concentration gradients across it, as well as by the physico-chemical properties of the substances. The barrier determines whether and how fast an administered drug enters the brain and how fast it will leave it as the blood level decreases. It also determines the access and egress of other substances such as metabolites and precursors.

The nature of the blood–brain barrier

The properties of the barrier arise as a consequence of the special properties of the capillary endothelium which separates the brain substance from the blood capillaries or the choroidal epithelium which separates the cerebro-spinal fluid (CSF) from the blood in the choroidal plexus. The cavities of the brain (cerebral ventricles) are filled with cerebro-spinal fluid (CSF), which differs only slightly in composition from the extracellular fluid surrounding the brain cells. The relationship between, blood, brain, extracellular fluid and the CSF is shown in Fig. 6.1.

The CSF is secreted by the choroidal plexus lining the cerebral ventricles.