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The blood–brain barrier is formed by special tight junctions between endothelial cells lining brain blood vessels. Blood vessels of all tissues contain this monolayer of endothelial cells, however only brain endothelial cells have tight junctions preventing passive diffusion of most substances into the brain tissue. [1]
The blood–brain barrier is formed by the brain capillary endothelium and excludes from the brain 100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs. [28] Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of most brain disorders.
The permeability of a capillary wall is determined by the type of capillary and the surface of the endothelial cells. A continuous, tightly spaced endothelial cell lining only permits the diffusion of small molecules. Larger molecules and blood cells require adequate space between cells or holes in the lining.
The cells of the neurovascular unit also make up the blood–brain barrier (BBB), which plays an important role in maintaining the microenvironment of the brain. [11] In addition to regulating the exit and entrance of blood, the blood–brain barrier also filters toxins that may cause inflammation, injury, and disease. [12]
These cells communicate with endothelial cells via gap junctions, and in turn cause endothelial cells to proliferate or be selectively inhibited. If this process did not occur, hyperplasia and abnormal vascular morphogenesis could result. These types of pericyte can also phagocytose exogenous proteins.
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Fibrinoid necrosis is a pathological lesion that affects blood vessels, and is characterized by the occurrence of endothelial damage, followed by leakage of plasma proteins, including fibrinogen, from the vessel lumen; these proteins infiltrate and deposit within the vessel walls, where fibrin polymerization subsequently ensues.
This process can ultimately form a uniform dispersion of small droplets in a fluid substance by subdividing particles until the desired consistency is acquired. [8] This manufacturing process is already scaled and in use in the food industry, which therefore makes it more appealing for researchers and for the drug delivery industry.