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Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro

Chaitanya, Ganta V.; Cromer, Walter E.; Wells, Shannon R.; Jennings, Merilyn H.; Couraud, P. Oliver; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, James Michael; Minagar, Alireza and Alexander, J. Steven (2011). Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro. Journal of Neuroinflammation, 8(162)

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The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of in vitro barrier integrity. We found that neither TNF-alpha, IL-1 beta or IFN-gamma directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs).

Item Type: Journal Item
Copyright Holders: 2011 Chaitanya et al. ; licensee BioMed Central Ltd.
ISSN: 1742-2094
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot SetPost‐doctoral fellowship support from the 'Feist Cardiovascular Research Endowment, LSUHSC‐Shreveport
Not SetNot SetNIH DK43785 grant
Keywords: TNF‐α; IL‐1β; IFN‐γ; brain endothelium; astrocytes; co‐culture; mono‐Culture
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
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Item ID: 30558
Depositing User: Ignacio A Romero
Date Deposited: 13 Dec 2011 16:31
Last Modified: 07 Dec 2018 09:58
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