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Here we report that<jats:italic>Lama2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, lacking expression of the laminin \u03b12 subunit of the laminin-211 heterotrimer expressed by astrocytes and pericytes, have a defective BBB in which systemically circulated tracer leaks into the brain parenchyma. The<jats:italic>Lama2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>vascular endothelium had significant abnormalities, including altered integrity and composition of the endothelial basal lamina, inappropriate expression of embryonic vascular endothelial protein MECA32, substantially reduced pericyte coverage, and tight junction abnormalities. Additionally, astrocytic endfeet were hypertrophic and lacked appropriately polarized aquaporin4 channels. Laminin-211 appears to mediate these effects at least in part by dystroglycan receptor interactions, as preventing dystroglycan expression in neural cells led to a similar set of BBB abnormalities and gliovascular disturbances, which additionally included perturbed vascular endothelial glucose transporter-1 localization. These findings provide insight into the cell and molecular changes that occur in congenital muscular dystrophies caused by<jats:italic>Lama2<\/jats:italic>mutations or inappropriate dystroglycan post-translational modifications, which have accompanying brain abnormalities, including seizures. Our results indicate a novel role for laminin\u2013dystroglycan interactions in the cooperative integration of astrocytes, endothelial cells, and pericytes in regulating the BBB.<\/jats:p>","DOI":"10.1523\/jneurosci.3678-13.2014","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T18:18:07Z","timestamp":1415816287000},"page":"15260-15280","source":"Crossref","is-referenced-by-count":233,"title":["The Extracellular Matrix Protein Laminin \u03b12 Regulates the Maturation and Function of the Blood\u2013Brain Barrier"],"prefix":"10.1523","volume":"34","author":[{"given":"Michael J.","family":"Menezes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freyja K.","family":"McClenahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-5341","authenticated-orcid":false,"given":"Cindy 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