4.1 Article

Astrocytic β1-integrin affects cellular composition of murine blood brain barrier in the cerebral cortex

Journal

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ijdevneu.2015.05.005

Keywords

Astrocytes; Endothelial cells; Transgenic; Brain; Hypoxia ischemia; Development

Funding

  1. Child Neurology Foundation Shields Award [RO1 NS200113, RO1 NS 20778]

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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. beta 1-integrin (beta 1-itg) within endothelial cells is known to play a critical role in vasculogenesis. However, the role of astrocytic beta 1-itg in BBB development is not known. Our study used a mouse glial fibrillary acidic protein (GFAP)-cre transgenic line to selectively ablate beta 1-itg within astrocytes. We found that deletion of astrocytic beta 1-itg had a striking effect on the different cell types that form the BBB. Mutant mice had a decreased density of aquaporin-4 immunoreactivity within the perivascular astrocytic end-feet. We also found decreases in immunoreactivity for vimentin and CD-31 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 beta 1-itg has an important role in defining cellular properties of the blood brain barrier in the cerebral cortex. (C) 2015 ISDN. Published by Elsevier Ltd. All rights reserved.

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