Expression of Heparanase in Vasculature Cells and Astrocytes of the Mouse Brain after Focal Cerebral Ischemia

• Type of Material: Article
• Authors: Jimei Li, Medical University of South Carolina; Jin-Ping Li, Uppsala University; Xiao Zhang, Uppsala University; Zhongyang Lu, Medical University of South Carolina; Shan Ping Yu, Emory University; Ling Wei, Emory University
• Language: English
• Date: 2012-01-18
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.brainres.2011.11.032
• Title of Journal or Parent Work: Brain Research
• ISSN: 0006-8993
• Volume: 1433
• Start Page: 137
• End Page: 144
• Grant/Funding Information: This work was supported by NIH grants NS057255, NS 058710, and NS062097.; This work was also supported by the National Natural Science Foundation of China (30772302) and Beijing Natural Science Foundation (7082029), as well as NIH grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources.
• Keywords: Heparanase; Angiopoietin-2; Cerebral ischemia; FGF-2; Angiogenesis; Astrocytes; Endothelial cells
• Research Categories: Biology, Neuroscience; Biology, Microbiology; Health Sciences, Pathology; Health Sciences, General

Abstract

Heparanase is a heparan sulfate degrading endoglycosidase. Previous work has demonstrated that heparanase plays important roles in various biological processes including angiogenesis, wound healing and metastasis. However, the role of heparanase in the post-ischemic brain is not well defined. Transient focal cerebral ischemia in adult mice was induced by ligations of the right middle cerebral artery (MCA) and both common carotid arteries (CCAs). All mice were subjected to bromodeoxyuridine (BrdU) injection and sacrificed at different time points after stroke for immunohistochemical and Western blot analyses. Heparanase expression increased after ischemia in both cell-specific and time-dependent manners. Three to 7 days after stroke, levels of the 50-kD heparanase, basic fibroblast growth factor (FGF-2), and angiopoietin-2 (Ang-2) increased in the peri-infarct region. At early time points, heparanase expression was largely confined to proliferating vascular endothelial cells. At 14 days after ischemia, this expression had shifted to astrocytes in the same region. These data show that cerebral ischemia markedly increases heparanase levels in endothelial cells and then in astrocytes. The unique features of the heparanase upregulation imply that heparanase may play specific roles in the pathological and regenerative processes during the acute and sub-acute/chronic phase in the post-stroke brain.