This Article Full Text Full Text (PDF) All Versions of this Article: 39/1/191    most recent STROKEAHA.107.486134v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Milner, R. Articles by del Zoppo, G. J. Search for Related Content PubMed PubMed Citation Articles by Milner, R. Articles by del Zoppo, G. J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB GLUCOSE OXYGEN Related Collections Receptor pharmacology Animal models of human disease Acute Cerebral Infarction Ischemic biology - basic studies Spinal Cord Vascular Disease

(Stroke. 2008;39:191.)
© 2008 American Heart Association, Inc.

Original Contributions

Responses of Endothelial Cell and Astrocyte Matrix-Integrin Receptors to Ischemia Mimic Those Observed in the Neurovascular Unit

Richard Milner, MD, PhD; Stephanie Hung, MS; Xiaoyun Wang, MS; Greta I. Berg, BS; Maria Spatz, MD Gregory J. del Zoppo, MD

From the Department of Molecular and Experimental Medicine (R.M., S.H., X.W., G.I.B., G.J.d.Z.), The Scripps Research Institute, La Jolla, Ca; Departments of Medicine and Neurology (G.J.d.Z.), University of Washington, Seattle, Wash; and the Stroke Branch (M.S.), National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md, USA.

Correspondence to Gregory J. del Zoppo, MD, Departments of Medicine and Neurology, University of Washington, at Harborview Medical Center, 325 Ninth Ave, Box 359756, Seattle, WA 98104. E-mail grgdlzop{at}u.washington.edu

Background and Purpose— Apposition of endothelial cells and astrocyte foot processes to the basal lamina matrix is postulated to underlie the cerebral microvessel permeability barrier. Focal cerebral ischemia induces rapid loss of select matrix-binding integrins from both cell compartments in the nonhuman primate. This study is the first to examine the conditions underlying integrin loss from these cell-types during ischemia in vitro and their relation to the changes in vivo.

Methods— The impact of normoxia or standardized oxygen-glucose deprivation on integrin expression by murine primary cerebral endothelial cells and astrocytes grown on matrix substrates (collagen IV, laminin, and perlecan) of the basal lamina were quantitatively assessed by flow cytometry.

Results— Endothelial cell expression of the β1 and 5 subunits significantly increased on all matrix ligands, whereas astrocytes displayed modest significant decreases in 5 and 6 subunits. Oxygen-glucose deprivation produced a further significant increase in subunit β1 expression by both cell types, but a clear decrease in both 1 and 6 subunits by murine astrocytes.

Conclusions— Ischemia in vitro significantly increased endothelial cell β1 expression, which is consistent with the increase in β1 transcription by microvessels peripheral to the ischemic core. The loss of 1 and 6 integrins from murine astrocytes is identical to that seen in the nonhuman primate in vivo. These findings establish both isolated murine cerebral endothelial cells and astrocytes as potential integrin response cognates of microvascular cells of the neurovascular unit in primates, and allow determination of the mechanisms of their changes to ischemia.

Key Words: astrocytes • endothelial cells • integrins • ischemic stroke • matrix