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Blood-brain Barrier Permeability

The Blood-brain barrier (BBB) is composed of a network of vessels that form a structural and chemical barrier between the brain and systemic circulation. Vessels of the BBB are composed of specialized endothelial cells that lack fenestration (pores that allow rapid exchange of molecules between vessels and tissue), have few pinocytic vesicles to minimize uptake of extracellular substances, and have extensive tight junctions that severely restrict cell permeability. Limited permeability restricts movement of substances from the systemic circulation to the brain which buffers the brain from rapid changes in ionic or metabolic conditions. Limited BBB permeability also protects the brain from exposure to molecules that are harmless to peripheral organs but toxic to neurons in the brain. BBB permeability is influenced by neurons, the extracellular matrix, and non-neuronal cells including astrocytes, pericytes, and vascular endothelial cells. These cells, along with the extracellular matrix, function as a neurovascular unit to regulate BBB permeability and maintain the integrity and function of the central nervous system.

Under normal physiological conditions, the neurovascular unit limits BBB permeability which prevents transport of bacteria, large molecules, and most small molecules into the brain. Entrance into the brain requires molecules to be lipid soluble, less than 400 Daltons, and not substrates of active efflux transporters (AET). Molecules that do not meet these requirements pass the blood brain barrier only if they are transported by carrier-mediated transporters (CMT) or through receptor-mediated transport (RMT). Waste products and small molecules that are too large or too hydrophilic to pass through the BBB only leave the brain as substrates of AET. However, under certain conditions such as inflammation, traumatic brain injury or ischemic stroke, the BBB is compromised allowing for the passage of larger and hydrophilic substances.