Abstract T P229: Expression of ECM-associated Genes in Rat Brains Following Experimental Intracerebral Hemorrhage
Background and purpose: Intracerebral hemorrhage (ICH) is a critical subtype of stroke. Destruction of blood brain barrier, formation of brain edema, are closely relevant to the change of extracellular matrix (ECM). The study is to investigate expression of ECM-associated genes, to provide new clues and ideas for exploring ICH treatment.
Methods: This study was divided into two parts. (1) ICH was induced by injecting type VII collagenase. Gene chip technology was used to detect genes related with ECM. (2) Laser confocal scanning microscopy was used to observed angioarchitecture and blood perfusion after fluorescein isothiocyanate (FITC)-dextran injection. Immunohistochemisty were used to identify proliferating cell nuclear antigen (PCNA)+/ von Willebrand factor+(vWF) nuclei, and the spatiotemporal distribution of collagen I, collagen III, collagenIV,MMP-2, MMP-9, MT1-MMP, integrin αvβ3 and integrin α5β1. The protein level of collagens,MMPs, integrin β3 and integrin α5 were evaluated by Western blot.
Results: Gene chip detection showed that ECM-related genes like most members of collagens, MMPs, intergrins have all Changed after ICH. FITC-dextran perfusion showed that the impaired blood perfusion around the hematoma increasd from 7 days to 21 days after ICH (P<0.01). Immunohistochemisty displayed that PCNA+/ vWF+ nuclei peaked at 14 days after ICH (P<0.01). Numerous collagens, MMPs or integrins -positive blood vessel could be detected around the hematoma. Western blot showed that the protein of collagens, MMPs, integrin β3 and integrin α5 all increased significantly at 4 days after ICH (P<0.05). Expression of collagenI and collagen III peaked at 14 days (P<0.05), while expression of collagen IV started to reduce from 14 days. Protein level of MMP-9 decreased from at 7 days (P<0.05), while the expression of MMP-2, MT1-MMP,integrin β3 and integrin α5 increased untill 14 days (P<0.05).
Conclusions: Expression of ECM-related genes changed after ICH, which suggested that altered interaction between cerebral microvessel and ECM following ICH can affect angiogenesis and brain tissue restoration.
Grants from NSFC (Grant Nos. 30873221, 81173175 and 81202625) and Project for New Century Excellent Talents (NCET-11-0522).
Author Disclosures: A. Yang: None. H. Cui: None. H. Zhou: Research Grant; Significant; NSFC-81202625. T. Tang: Research Grant; Significant; NSFC (30873221, 81173175) and Project for New Century Excellent Talents (NCET-11-0522).
- © 2014 by American Heart Association, Inc.