Blood–brain barrier and monoamines, revisited

Introduction At the present time, it is generally accepted that the blood-brain barrier (BBB) represents a conglomeration of regulatory systems concerned with maintaining a homeostatic biochemical environment for the brain parenchyma. The concept of a barrier between the blood and brain originated almost a century ago with Ehrlich's studies demonstrating that injection of certain aniline dyes stained peripheral organs and tissues but not the brain (Ehrlich, 1902). This notion was expanded by Goldman (1909) who showed that directly injecting vital dyes into the cerebrospinal fluid (CSF) stained the entire brain without affecting peripheral organs and tissues. Notably, Goldman was the first to suggest that intraparenchymatous cerebral capillaries play a role in restricting the passage of the dyes between the blood and the brain or vice versa. The morphological confirmation for existence of the BBB at the level of brain capillaries was demonstrated by electron microscopy (Reese and Karnovsky, 1967). It has been shown that the endothelial cells, which comprise the brain capillaries and microvessels but not those in the peripheral vasculature, are connected by continuous belts of tight junctions, devoid of fenestrae and containing a few vesicles. Interestingly, the micro vascular endothelium of the choroid plexus and circumventricular organs lack these properties; the blood- CSF barrier of the choroid plexus is formed by tight junctions between epithelial cells (Lindvall et al ., 1980; Rapoport, 1976).