The blood-brain barrier (BBB) refers to the specialized vasculature that provides the brain with nutrients in the blood while strictly regulating the movement of ions, molecules, pathogens, and other substances. It is composed of tightly linked endothelial cells on one side and astrocyte projections on the other. Together they provide a semipermeable barrier that protects the brain and poses unique challenges to the delivery of therapeutics.
The BBB is made up of a variety of cellular components, including endothelial cells and astrocytes. These cells share a common basement membrane and together regulate the passage of components between the circulation and the interstitial fluid surrounding the brain.
The first type of cellular component, specialized endothelial cells, make up the walls of the cerebral capillaries. They are connected by extremely tight and complex intercellular junctions. These junctions create a selective physical barrier, preventing simple diffusion of most substances, including average to large-sized molecules such as glucose and insulin.
A second cell type, astrocytes, are a type of glial cell of the central nervous system which influences endothelial cell function, blood flow, and ion balance in the brain through interaction and close association with cerebral vasculature. They provide a direct link between the vasculature and neurons: they extend processes—called endfeet—that wrap around blood vessels on one end while making intimate contact with neurons at synapses on the other end.
The ability of a substance to cross the BBB and the efficiency with which this exchange occurs depends on the chemical and molecular properties of each molecule or ion. In general, small lipid-soluble components, such as oxygen and carbon dioxide, undergo rapid, simple diffusion through the endothelial layer. In contrast, larger or water-soluble components often require a more selective process that may involve passive or active transport through an endothelial cell. The exchange of these substances generally occurs more slowly or may not occur at all, depending on the relative abundance and efficiency of molecule-specific receptors and transport proteins on the surface of endothelial cells, among other factors.
The neural protection facilitated by the BBB is critical to proper brain health and function. Dysregulation of the BBB can lead to severe neurological disease including multiple sclerosis, infection, and ischemia due to an inadequate blood supply. Conversely, the activity of the BBB may be detrimental to the treatment of some neurologic diseases by preventing or substantially reducing the passage of neuroactive pharmaceutical drugs into the central nervous system. For this reason, drugs with neurological targets must be designed in a way that facilitates passage through the BBB.
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