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Publication : Deletion of astroglial connexins weakens the blood-brain barrier.

First Author  Ezan P Year  2012
Journal  J Cereb Blood Flow Metab Volume  32
Issue  8 Pages  1457-67
PubMed ID  22472609 Mgi Jnum  J:315134
Mgi Id  MGI:6822399 Doi  10.1038/jcbfm.2012.45
Citation  Ezan P, et al. (2012) Deletion of astroglial connexins weakens the blood-brain barrier. J Cereb Blood Flow Metab 32(8):1457-67
abstractText  Astrocytes, the most prominent glial cell type in the brain, send specialized processes named endfeet, which enwrap blood vessels and express a large molecular repertoire dedicated to the physiology of the vascular system. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein connexins 43 and 30 (Cx43 and Cx30) allowing for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. The contribution of astroglial connexins to the physiology of the brain vascular system has never been addressed. Here, we show that Cx43 and Cx30 expression at the level of perivascular endfeet starts from postnatal days 2 and 12 and is fully mature at postnatal days 15 and 20, respectively, indicating that astroglial perivascular connectivity occurs and develops during postnatal blood-brain barrier (BBB) maturation. We demonstrate that mice lacking Cx30 and Cx43 in GFAP (glial fibrillary acidic protein)-positive cells display astrocyte endfeet edema and a partial loss of the astroglial water channel aquaporin-4 and beta-dystroglycan, a transmembrane receptor anchoring astrocyte endfeet to the perivascular basal lamina. Furthermore, the absence of astroglial connexins weakens the BBB, which opens upon increased hydrostatic vascular pressure and shear stress. These results demonstrate that astroglial connexins are necessary to maintain BBB integrity.
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