The BBB is not one single structure or membrane in the brain, but it is created by the way the blood vessels in the brain are organized. Thus, understanding the BBB requires an understanding of the anatomy and physiology of the blood vessels in the brain. Both large and small capillaries form a richly branched and complex network throughout the entire brain tissue. Like a chimney made of individual bricks, the brain blood vessels consist of a monolayer of endothelial cells that are connected with each other by tight junctions (zonulae occludentes) . The part of the cell's membrane facing the bloodstream is called the "luminal" membrane [9-11], and the side which is exposed to the actual brain tissue is called the "abluminal" membrane. This part faces the extracellular liquid of the brain parenchyma where pericytes and endfeet of astrocytes surround the blood vessels.
The most important site of the BBB lies at the cerebral microvessels, that is, the very fine vessels that have extremely small diameters. Because endothelial cells are very polarized, that is, essentially similar to the epithelium, they exhibit very low pinocytic activity and possess a high number of mitochondria that are needed for the multiple energy-dependent active transport mechanisms found in endothelial cells .
Peripheral vessels in the rest of the body can much more easily transport molecules across their membrane because they are fenestrated and have many active tran-scellular transport mechanisms. In contrast, in central blood vessels of the brain, even small molecules like antibiotics have great difficulty crossing the barrier and only a limited number of molecules can actively cross the endothe-lial cells. Here, the endothelial cells use specific transport systems to allow the influx of glucose, iron, amino acids, peptides, small organic acids, and others. This is necessary so that substances which are critical for brain metabolism and function can gain fast and efficient access to the brain via specific energy-dependent carrier mechanisms at the endothelium .
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