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Blood–brain barrier
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==Structure== [[File:Blood Brain Barriere.jpg|thumb|Astrocytes surrounding capillaries in the brain]] [[File:Blood vessels brain english.jpg|thumb|Sketch showing constitution of blood vessels inside the brain]] The BBB results from the selectivity of the [[tight junctions]] between the endothelial cells of brain capillaries, restricting the passage of solutes.<ref name=daneman/> At the interface between blood and the brain, endothelial cells are adjoined continuously by these tight junctions, which are composed of smaller subunits of [[transmembrane protein]]s, such as [[occludin]], [[claudins]] (such as [[CLDN5|Claudin-5]]), [[junctional adhesion molecule]] (such as JAM-A).<ref name="Stamatovic 2008 179–192"/> Each of these tight junction proteins is stabilized to the endothelial cell membrane by another protein complex that includes scaffolding proteins such as [[tight junction protein 1]] (ZO1) and associated proteins.<ref name="Stamatovic 2008 179–192"/> The BBB is composed of endothelial cells restricting passage of substances from the blood more selectively than endothelial cells of capillaries elsewhere in the body. [[Astrocyte]] cell projections called astrocytic feet (also known as "[[glia limitans]]") surround the endothelial cells of the BBB, providing biochemical support to those cells.<ref>{{cite journal | vauthors = Abbott NJ, Rönnbäck L, Hansson E | s2cid = 205500476 | title = Astrocyte-endothelial interactions at the blood-brain barrier | journal = Nature Reviews. Neuroscience | volume = 7 | issue = 1 | pages = 41–53 | date = January 2006 | pmid = 16371949 | doi = 10.1038/nrn1824 }}</ref> The BBB is distinct from the quite similar [[Choroid plexus#Function|blood-cerebrospinal fluid barrier]], which is a function of the choroidal cells of the [[choroid plexus]], and from the [[blood-retinal barrier]], which can be considered a part of the whole realm of such barriers.<ref>{{cite journal | vauthors = Hamilton RD, Foss AJ, Leach L | title = Establishment of a human in vitro model of the outer blood-retinal barrier | journal = Journal of Anatomy | volume = 211 | issue = 6 | pages = 707–16 | date = December 2007 | pmc = 2375847 | doi = 10.1111/j.1469-7580.2007.00812.x | pmid = 17922819 }}{{open access}}</ref> Not all vessels in the human brain exhibit BBB properties. Some examples of this include the [[circumventricular organs]], the roof of the third and fourth [[ventricular system|ventricles]], capillaries in the pineal gland on the roof of the [[diencephalon]] and the [[pineal gland]].<ref name=peering/><ref name=gross1/> ===Development=== The BBB appears to be functional by the time of birth. [[P-glycoprotein]], a [[ATP-binding cassette transporter|transporter]], exists already in the embryonal endothelium.<ref>{{cite journal | vauthors = Tsai CE, Daood MJ, Lane RH, Hansen TW, Gruetzmacher EM, Watchko JF | s2cid = 46815691 | title = P-glycoprotein expression in mouse brain increases with maturation | journal = Biology of the Neonate | volume = 81 | issue = 1 | pages = 58–64 | date = January 2002 | pmid = 11803178 | doi = 10.1159/000047185 }}</ref> Measurement of brain uptake of various blood-borne solutes showed that newborn endothelial cells were functionally similar to those in adults,<ref name="Braun 2006 147–152">{{cite journal | vauthors = Braun LD, Cornford EM, [[William H. Oldendorf|Oldendorf WH]] | title = Newborn rabbit blood-brain barrier is selectively permeable and differs substantially from the adult | journal = Journal of Neurochemistry | volume = 34 | issue = 1 | pages = 147–52 | date = January 1980 | pmid = 7452231 | doi = 10.1111/j.1471-4159.1980.tb04633.x | s2cid = 21944159 }}</ref> indicating that a selective BBB is operative at birth.
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