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One of the fundamental functions of the blood-brain barrier (BBB) is to regulate the movement of essential metabolites within the central nervous system (CNS)(1). The BBB is made up of a continuous layer of endothelial cells that are circumferentially joined by tight junctions (2). Its integrity is maintained by precise interactions between endothelial cells, pericytes, microglia, astrocytes, and neurons (2). Unrestricted interlinkage and communication between these cells are necessary for the proper regulation and operation of the BBB. Transport across the BBB can be passive, transcellularly through junctional adhesion molecules and accessory proteins such as ZO-1, claudins, occludins, and active through transporters and carriers expressed on the luminal BBB architecture (3). While the semi-permeable nature of the BBB is crucial in a healthy physiological state, therapeutic delivery to the brain can be highly limited.

Drugs that have shown success in treating peripheral diseases frequently fail when used to treat CNS diseases and disorders (4). Efforts to overcome the limited brain distribution of therapeutics have paired personalized targeted medicines with local delivery strategies. However, these efforts have limited clinical success (3, 5). An emerging method to achieve therapeutically effective drug concentrations within the CNS involves disruptive techniques for transient opening of the BBB such as focused ultrasound, radiation or osmotic reagents (6).