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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-36013

Al Ahmad, A; Taboada, C B; Gassmann, M; Ogunshola, O O (2011). Astrocytes and pericytes differentially modulate blood-brain barrier characteristics during development and hypoxic insult. Journal of Cerebral Blood Flow and Metabolism, 31:693-705.

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Abstract

Understanding regulation of blood-brain barrier (BBB) is crucial to reduce/prevent its disruption during injury. As high brain complexity makes interpretation of in vivo data challenging, BBB studies are frequently performed using simplified in vitro models. However, many models fail to address the three-dimensional (3D) cellular interactions that occur in vivo, an important feature that may explain discrepancies in translation of in vitro data to the in vivo situation. We have designed and characterized an innovative 3D model that reproduces morphological and functional characteristics of the BBB in vivo and used it to investigate cellular interactions and contribution of astrocytes and pericytes to BBB development. Our model shows that both astrocytes and pericytes significantly suppress endothelial proliferation. In contrast, differential effects on tubulogenesis were observed with astrocytes reducing the number of tubes formed but increasing diameters and length, whereas pericytes had the opposite effect. Pericytes also induce proper localization of barrier proteins, lumen polarization, and functional activity of ATP-binding cassette (ABC) transporters similar to astrocytes, but the presence of both cells is required to maintain optimal barrier characteristics during hypoxic exposure. This model is simple, dynamic, and convenient to study many aspects of BBB function and represents an exciting new tool to address open questions of BBB regulation.Journal of Cerebral Blood Flow & Metabolism advance online publication, 8 September 2010; doi:10.1038/jcbfm.2010.148.

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27 citations in Web of Science®
33 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > Center for Integrative Human Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:11 Nov 2010 12:41
Last Modified:27 Nov 2013 17:12
Publisher:Nature Publishing Group
ISSN:0271-678X
Publisher DOI:10.1038/jcbfm.2010.148
PubMed ID:20827262

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