{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:20:57Z","timestamp":1790356857105,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T00:00:00Z","timestamp":1431993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006457","name":"Child Neurology Foundation","doi-asserted-by":"publisher","award":["RO1 NS200113"],"award-info":[{"award-number":["RO1 NS200113"]}],"id":[{"id":"10.13039\/100006457","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006457","name":"Child Neurology Foundation","doi-asserted-by":"publisher","award":["RO1 NS 20778"],"award-info":[{"award-number":["RO1 NS 20778"]}],"id":[{"id":"10.13039\/100006457","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The blood brain barrier (BBB) is composed of endothelial cells, astrocytes, and pericytes and maintains functional homeostasis by regulating transport of ions, fluid and cells between blood and neural tissue. The cellular and molecular pathways that contribute to the formation of the BBB in the developing brain have not been fully deciphered. \u03b21\u2010integrin (\u03b21\u2010itg) within endothelial cells is known to play a critical role in vasculogenesis. However, the role of astrocytic \u03b21\u2010itg in BBB development is not known. Our study used a mouse glial fibrillary acidic protein (GFAP)\u2010cre transgenic line to selectively ablate \u03b21\u2010itg within astrocytes. We found that deletion of astrocytic \u03b21\u2010itg had a striking effect on the different cell types that form the BBB. Mutant mice had a decreased density of aquaporin\u20104 immunoreactivity within the perivascular astrocytic end\u2010feet. We also found decreases in immunoreactivity for vimentin and CD\u201031 within endothelial cells. These changes were not accompanied by functional changes in BBB under physiological conditions as assessed by extravasation of large and small molecular weight molecules. However, mutant mice had an increased incidence of severe cystic injury in response to neonatal hypoxia. Our findings show that astrocytic \u03b21\u2010itg has an important role in defining cellular properties of the blood brain barrier in the cerebral cortex.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2015.05.005","type":"journal-article","created":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T22:01:40Z","timestamp":1432072900000},"page":"48-54","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Astrocytic \u03b21\u2010integrin affects cellular composition of murine blood brain barrier in the cerebral cortex"],"prefix":"10.1002","volume":"44","author":[{"given":"Charu","family":"Venkatesan","sequence":"first","affiliation":[{"name":"Department of Pediatrics Division of Neurology Ann &amp; Robert H. Lurie Children's Hospital of Chicago Chicago IL 60611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derin","family":"Birch","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago IL 60611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chian\u2010yu","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago IL 60611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Kessler","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago IL 60611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,19]]},"reference":[{"issue":"6","key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1528-1167.2012.03696.x","article-title":"Overview and introduction: the blood\u2013brain barrier in health and disease","volume":"53","author":"Abbott N.J.","year":"2012","journal-title":"Epilepsia"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.3.435"},{"issue":"12","key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1242\/dev.016378","article-title":"Cell\u2010autonomous requirement for beta1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice","volume":"135","author":"Carlson T.R.","year":"2008","journal-title":"Development"},{"issue":"1","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1093\/hmg\/ddt400","article-title":"Tbx1 regulates brain vascularization","volume":"23","author":"Cioffi S.","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00032-3"},{"issue":"5","key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/ana.23648","article-title":"The blood\u2013brain barrier in health and disease","volume":"72","author":"Daneman R.","year":"2012","journal-title":"Ann. Neurol."},{"issue":"5","key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/jcbfm.2014.255","article-title":"Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia\u2010ischemia","volume":"35","author":"Ek C.J.","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"issue":"28","key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"9588","DOI":"10.1523\/JNEUROSCI.5977-11.2012","article-title":"Blood brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat","volume":"32","author":"Fernandez\u2010Lopez D.","year":"2012","journal-title":"J. Neurosci."},{"issue":"1","key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.devbrainres.2004.05.008","article-title":"Endothelial cell\u2010astrocyte interactions and TGF beta are required for induction of blood\u2013neural barrier properties","volume":"152","author":"Garcia C.M.","year":"2004","journal-title":"Brain Res. Dev. Brain Res."},{"issue":"6","key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1172\/JCI23445","article-title":"Integrin alpha4beta1\u2010VCAM\u20101\u2010mediated adhesion between endothelial and mural cells is required for blood vessel maturation","volume":"115","author":"Garmy\u2010Susini B.","year":"2005","journal-title":"J. Clin. Invest."},{"issue":"28","key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"7231","DOI":"10.1523\/JNEUROSCI.1709-08.2008","article-title":"STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury","volume":"28","author":"Hermann J.E.","year":"2008","journal-title":"J. Neurosci."},{"issue":"6","key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","article-title":"Integrins: bidirectional, allosteric signaling machines","volume":"110","author":"Hynes R.O.","year":"2002","journal-title":"Cell"},{"issue":"43","key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"33920","DOI":"10.1074\/jbc.M003668200","article-title":"Regulation of integrin alpha vbeta 3\u2010mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase A","volume":"275","author":"Kim S.","year":"2000","journal-title":"J. Biol. Chem."},{"issue":"1","key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.yexcr.2004.12.023","article-title":"The intermediate filament protein vimentin binds specifically to a recombinant integrin alpha2\/beta1 cytoplasmic tail complex and co\u2010localizes with native alpha2\/beta1 in endothelial cell focal adhesions","volume":"305","author":"Kreis S.","year":"2005","journal-title":"Exp. Cell Res."},{"issue":"17","key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"4622","DOI":"10.1111\/j.1742-4658.2009.07174.x","article-title":"Brain angiogenesis in developmental and pathological processes: regulation, molecular and cellular communication at the neurovascular interface","volume":"276","author":"Lee H.S.","year":"2009","journal-title":"FEBS J."},{"issue":"4","key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1387\/ijdb.103224sl","article-title":"Current concepts of blood\u2013brain barrier development?","volume":"55","author":"Liebner S.","year":"2011","journal-title":"Int. J. Dev. Biol."},{"issue":"2","key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"C363","DOI":"10.1152\/ajpcell.00057.2010","article-title":"Regulation of vimentin intermediate filaments in endothelial cells by hypoxia","volume":"299","author":"Liu T.","year":"2010","journal-title":"Cell Physiol."},{"issue":"3","key":"e_1_2_6_19_1","first-page":"163","article-title":"Ultrastructural studies of PECAM\u20101\/CD31 expression in the developing mouse blood\u2013brain barrier with the application of a pre\u2010embedding technique","volume":"35","author":"Lossinsky A.S.","year":"1997","journal-title":"Folia Neuropathol."},{"issue":"10","key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"e48001","DOI":"10.1371\/journal.pone.0048001","article-title":"A functional requirement for astroglia in promoting blood vessel development in the early postnatal brain","volume":"7","author":"Ma S.","year":"2012","journal-title":"PLoS One"},{"issue":"5","key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S0896-6273(03)00116-8","article-title":"Neuronal or glial progeny: regional differences in radial glia fate","volume":"37","author":"Malatesta P.","year":"2003","journal-title":"Neuron"},{"issue":"3","key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1083\/jcb.85.3.890","article-title":"Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue","volume":"85","author":"McCarthy K.D.","year":"1980","journal-title":"J. Cell Biol."},{"issue":"1","key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jneumeth.2011.08.002","article-title":"A new method for visualization of endothelial cells and extravascular leakage in adult mouse brain using fluorescein isothiocyanate","volume":"202","author":"Miyata S.","year":"2011","journal-title":"J. Neurosci. Methods"},{"issue":"1","key":"e_1_2_6_24_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1523\/JNEUROSCI.17-01-00171.1997","article-title":"Specialized membrane domains for water transport in glial cells: high\u2010resolution immunogold cytochemistry of aquaporin\u20104 in rat brain","volume":"17","author":"Nielsen S.","year":"1997","journal-title":"J. Neurosci."},{"issue":"3","key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.neuron.2011.07.013","article-title":"The neurovascular link in health and disease: molecular mechanisms and therapeutic implications","volume":"71","author":"Quaegebeur A.","year":"2011","journal-title":"Neuron"},{"issue":"15","key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1002\/glia.20876","article-title":"Conditional deletion of beta1\u2010integrin in astroglia causes partial reactive gliosis","volume":"57","author":"Robel S.","year":"2009","journal-title":"Glia"},{"issue":"25","key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"13612","DOI":"10.1073\/pnas.94.25.13612","article-title":"Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins","volume":"94","author":"Senger D.R.","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"2","key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0168-0102(99)00079-6","article-title":"Induction of blood\u2013brain barrier properties in immortalized bovine brain endothelial cells by astrocytic factors","volume":"35","author":"Sobue K.","year":"1999","journal-title":"Neurosci. Res."},{"issue":"12","key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","article-title":"Molecular dissection of reactive astrogliosis and glial scar formation","volume":"32","author":"Sofroneiw M.V.","year":"2009","journal-title":"Trends Neurosci."},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4413"},{"issue":"2","key":"e_1_2_6_31_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2008.01.003","article-title":"The blood\u2013brain barrier in health and chronic neurodegenerative disorders","volume":"57","author":"Zlokovic B.V.","year":"2008","journal-title":"Neuron"}],"container-title":["International Journal of Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S073657481500413X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S073657481500413X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.ijdevneu.2015.05.005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2015.05.005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.ijdevneu.2015.05.005","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2015.05.005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T12:27:18Z","timestamp":1694003238000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1016\/j.ijdevneu.2015.05.005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,19]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1016\/j.ijdevneu.2015.05.005"],"URL":"https:\/\/doi.org\/10.1016\/j.ijdevneu.2015.05.005","archive":["Portico"],"relation":{},"ISSN":["0736-5748","1873-474X"],"issn-type":[{"value":"0736-5748","type":"print"},{"value":"1873-474X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,19]]},"assertion":[{"value":"2015-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}