Blood brain barrier tight junctions

Dallasta LM, Pisarov LA, Esplen JE, Werley JV, Moses AV, Nelson JA, Achim CL (1999) Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. Am J Pathol 155 1915-1927... 

Kniesel U, Risau W, Wolburg H (1996) Development of blood-brain barrier tight junctions in the rat cortex. Develop Brain Res 96 229-240... 

Huber JD, Hau VS, Borg L, Campos CR, Egleton RD, Davis TP (2002) Blood-brain barrier tight junctions are altered during a 72-h exposure to lamba-carrageenan-induced inflammatory pain. Am J Physiol 283 H1531-H1537. 

Tight junctions between endothelial cells of blood capillaries in the brain prevent free diffusion of compounds from the blood stream into brain cells and form the blood-brain barrier. Tight junctions between neurons and adjacent cells surround the nodes of Ranvier (Chapter 30). 

Pfeiffer F, Schafer J, Lyck R et al (2011) Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis. Acta Neuropathol 122 601-614... 

Specific barriers may serve to limit dmg distribution. The placental barrier is of obvious importance to dmg action in the fetus. Dmg transfers across the placenta primarily by Hpid solubiHty. Hence, this barrier is not particularly restrictive. Similarly, the Hpid solubiHty of a dmg is a primary deterrninant in access to the brain and cerebrospinal fluid. Generally, hydrophilic or charged dmgs can also penetrate to these latter areas, but the result is slow and incomplete. The blood brain barrier is composed of cells having tight junctions which are much less permeable to solutes than are the endotheHal cells of other tissues. 

The blood-brain barrier (BBB) forms a physiological barrier between the central nervous system and the blood circulation. It consists of glial cells and a special species of endothelial cells, which form tight junctions between each other thereby inhibiting paracellular transport. In addition, the endothelial cells of the BBB express a variety of ABC-transporters to protect the brain tissue against toxic metabolites and xenobiotics. The BBB is permeable to water, glucose, sodium chloride and non-ionised lipid-soluble molecules but large molecules such as peptides as well as many polar substances do not readily permeate the battier. 

FIGURE 29-1. The blood-brain barrier selectively inhibits certain substances from entering the interstitial spaces of the brain and spinal fluid. It is thought that certain cells within the brain form tight junctions that prevent or slow the passage of certain substances. Levodopa passes the blood-brain barrier, whereas dopamine is unable to pass. 

Fig. 15.3 D iagram showing a longitudinal cross-section of the blood-brain barrier, with the brain capillary endothelial cells sealed by the tight junctions and surrounded by pericytes and astrocyte foot processes. These cellular components of the BBB are separated by a basement membrane.

Tight Junctions, Receptors and Cell Cross-Talk at the Blood-Brain Barrier... 

Kniesel U, Wolburg H. Tight junctions of the blood-brain barrier. Cell Mol Neu-robiol 2000 20 57-76. 

The blood-brain barrier forms the interface between the bloodstream and the brain parenchyma and thus controls the passage of endogenous substances and xenobiotics into and out of the central nervous system. Brain microvessels exhibit a variety of unique structural features, such as an extremely tight endothelium without fenestration, a very low rate of pinocytosis, tight junctions between endothelial cells excluding paracellular permeability, and a series of polarized transport proteins. The following chapter describes the structural and functional characteristics of the blood-brain barrier with emphasis on transport proteins, as well as in vitro techniques, which allow studying this complex barrier in the brain. 

The blood-brain barrier is markedly different from peripheral capillaries Peripheral capillaries are fenestrated with openings up to 50 nm wide. In contrast, cerebral endothelial cells are closely connected by tight junctions and zonulae occludentes, resulting in extremely high transendothelial resistances of up to 1500-2000 12 cm2 [16] (Figure 17.1). The capillaries are surrounded by a basal membrane enclosing intermittently pericytes, which have been postulated to be involved in host defense. The outer surface of the basement membrane is covered by astrocytic foot processes. Most likely, secretion of soluble growth factors by astrocytes plays an important role in endothelial cell differentiation. 

Freshly isolated or subcultured brain microvascular endothelial cells offer a notable in vitro tool to study drug transport across the blood-brain barrier. Cells can be grown to monolayers on culture plates or permeable membrane supports. The cells retain the major characteristics of brain endothelial cells in vivo, such as the morphology, specific biochemical markers of the blood-brain barrier, and the intercellular tight junctional network. Examples of these markers are y-glutamyl transpeptidase, alkaline phosphatase, von-Willebrandt factor-related antigen, and ZO-1 tight junctional protein. The methods of... 

Williams H, Neuhaus J, Kniesel U, KrauB B, Schmid E-M, Ocalan M, Farell C, Risau W (1980) Modulation of tight junction structure in blood-brain barrier endothelial cells. J Cell Sci 107 1347-1357... 

Blood-brain barrier a barrier created by tight junctions among cells of the brain capillaries that limits the movement of substances in the blood into the brain. 

Major differences between a general (nonneural) and brain capillary. In the brain capillary, the Intercellular clefts are sealed shut by tight Junctions. There are also reduced pinocytosis and no fenestrae. Exchange of compounds between the circulation and the brain must take place in the cells of the capillary wall, the major barriers of which are the inner and outer plasma membranes of the capillary endothelial cells. (Reprinted with permission from Oldendorf WA. Permeability of the blood-brain barrier. In Tower DB [ed.]. The Nervous System. Vol. 1 New York Raven, 1975.)... 

Figure 3.9 The blood-brain barrier (BBB) is a major impediment to the delivery of drugs to the brain. In the brain, in order for a drug molecule to leave a capillary and snccessfnlly jonmey to a neuronal receptor, it must traverse multiple barriers. The walls of capillaries in the brain are different from those in non-brain tissnes. Tight junctions prevent the drugs from readily crossing the capillary. Next, in the brain, another type of cell, called an astrocyte, forms an additional barrier that must be traversed. Astrocytes are not present outside of the brain.

Wolburg, H., et al. 2003. Localisation of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol 105 586. 

Hamm, S., et al. 2004. Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with loss of tight junction proteins from the cellular contacts. Cell Tissue Res 315 157. 

Bauer, H.C., A. Traweger, and H. Bauer. 2004. Proteins of the tight junction in the blood brain barrier. In Blood-spinal cord and brain barriers in health and disease, eds. H.S. Sharma and J. Westman, 1. San Diego Elsevier. 

Bolton, S.J., D.C. Anthony, and V.H. Perry. 1998. Loss of tight junction proteins occluding and zonula-occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86 1245. 

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