The blood-brain barrier: a focus on neurovascular unit components

The blood–brain barrier (BBB) provides an optimum environment for neurons by ensuring the integrity and homeostasis of highly fragile brain cells under physiological conditions, protecting the brain from changes in the blood with both structural (tight junctions) and metabolic (enzymes) barriers, selective transport, and the metabolism and modification of substances in the blood and brain. The endothelial cells of the brain capillaries, located at the interfaces between the blood and the brain, are critical components that limit the permeability of the BBB. These cells have unique morphological, biochemical, and functional characteristics that distinguish them from those found in the peripheral vascular system. In addition to endothelial cells, astrocytic perivascular end-feet, pericytes, neurons, microglia, and smooth muscle cells also play significant roles in maintaining the homeostasis of the brain parenchyma. Thus, the BBB effectively prevents various molecules and therapeutic drugs from entering the brain parenchyma and reaching the target area at sufficiently high concentrations. The passage of a substance through the BBB and its entry into the brain depends on various factors, including the substance’s lipophilicity, diffusion capability, molecular weight, electrical charge, blood concentration, and multiple primary and secondary factors. Drug delivery systems developed in recent years, through techniques and methods aimed at controlled and safe opening or bypassing of the BBB, are believed to provide significant benefits in the lesion area by allowing therapeutic substances to optimally enter the brain from the circulation. This article provides a review of the BBB and its components, highlighting their significance among the brain’s different interfaces. It also discusses approaches for delivering therapeutic substances to the affected area under optimal conditions and concentrations in various brain pathologies.