Abstract
Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no differences in cerebrovascular anatomy or collateral blood flow were noted that could account for this difference in ischemic injury. Rather, we demonstrate that α5 KOs have increased blood-brain barrier integrity (increased expression of claudin-5, and absent brain parenchymal IgG extravasation) after stroke compared with controls, which could explain their resistance to ischemic injury. Additionally, inhibition of α5 integrin in vitro leads to decreased permeability of brain endothelial cells following oxygen-glucose deprivation. Together, these findings indicate endothelial cell α5 integrin plays an important role in stroke outcome and blood-brain barrier integrity, suggesting that α5 integrin could be a novel therapeutic target for stroke.
Document Type
Article
Publication Date
11-13-2015
Digital Object Identifier (DOI)
https://doi.org/10.1177/0271678X15616979
Funding Information
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NIH 2R01NS065842-08 to G.J.B.
Repository Citation
Roberts, Jill; de Hoog, Leon; and Bix, Gregory J., "Mice Deficient in Endothelial α5 Integrin are Profoundly Resistant to Experimental Ischemic Stroke" (2015). Sanders-Brown Center on Aging Faculty Publications. 84.
https://uknowledge.uky.edu/sbcoa_facpub/84
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Family, Life Course, and Society Commons, Geriatrics Commons, Medical Neurobiology Commons, Neurology Commons
Notes/Citation Information
Published in Journal of Cerebral Blood Flow & Metabolism, v. 37, issue 1, p. 85-96.
© Author(s) 2015
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(https://us.sagepub.com/en-us/nam/open-access-at-sage).