Structure of the Blood Brain Barrier and the Role of Transporters in the movement of substrates across the barriers

Abstract

The blood brain barrier present in brain capillaries constitutes an essential barrier mechanism for normal functioning and development of the brain of structural integrity besides neuronal function. The structure and function of the BBB are summarised besides the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms. The presence of tight junctions between adjacent endothelial cells restricts the permeability and movement of molecules between extracellular fluid and plasma. It is divided into luminal and abluminal where each solute must cross both membranes. The roles of the neurovascular unit are outlined, especially the astrocyte endfeet, pericytes, and microglia. Five different systems of facilitative transport are found in the luminal membrane and are specific for a few substrates. Nonetheless, two major facilitative carriers (System L and y+) are located in both membranes asymmetrically. In contrast, several Na+ dependent transport systems transport amino acids against its concentration gradient present in the abluminal membrane, where the sodium pump Na+/K+-ATPase is highly expressed. The trojan horse mechanism is also favoured in drug delivery by employing molecular tools to bind the drug and its formulations. In the current work, we have revised the prevailing knowledge on the cellular structure of the BBB and the transport systems present exclusively for each substrate, and the need to find transporters with modifications that facilitate the transport of various drugs. Nevertheless, the blending of the classical pharmacology with nanotechnology needs to be focussed on promising results to rule out the BBB passage for the new generation of neuroactive drugs.