Blood—Brain Barrier Permeability to Peptides and Proteins
The neurons, glial cells, brain extracellular fluid and cerebrospinal fluid are separated from the blood by the blood-brain and blood-cerebrospinal fluid barriers (Davson, 1976). The blood-brain barrier is well characterized morphologically as a complete and continuous cellular layer of the endothelial cells which are sealed by tight junctions (Brightman, 1977). Normal cell-to-cell communications between astrocytes, pericytes, endothelial cells and surrounding neuropil are essential for the expression of blood-brain barrier phenomena and its homoeostatic mechanisms (Davson and Oldendorf, 1967; Brightman, 1989). Transport, enzymatic and receptor-mediated functions of the blood-brain barrier and blood-cerebrospinal fluid barrier are highly developed, playing a central role in the regulation of the composition of brain extracellular fluid and cerebrospinal fluid. The free movement of circulating hydrophilic substrates from blood to brain extracellular and cerebrospinal fluids is markedly retarded, and it has been accepted that any molecule, above a limiting size, circulating in the blood may gain access to the brain interstitial space only if there is a specific transport system for that molecule localized in the brain capillary endothelium (Oldendorf, 1987; Betz and Goldstein, 1986; Pardridge, 1988).
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