The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats

• Type of Material: Article
• Authors: A-M Buga, University of Greifswald; M Sascau, University of Greifswald; C Pisoschi, University of Medicine and Pharmacy; J Emmett Herndon, Emory University; C Kessler, University of Greifswald; A Popa-Wagner, University of Greifswald
• Language: English
• Date: 2008-12-02
• Publisher: Wiley Open Access
• Publication Version: Final Published Version
• Copyright Statement: © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/j.1582-4934.2008.00252.x
• Title of Journal or Parent Work: Journal of Cellular and Molecular Medicine
• ISSN: 1582-1838
• Volume: 12
• Issue: 6b
• Start Page: 2731
• End Page: 2753
• Grant/Funding Information: This research was supported by a grant from Bundesministerium fuer Bildung und Forschung to Aurel Popa-Wagner.
• Keywords: stroke; gene expression; rat; aging
• Research Categories: Biology, Neuroscience

Abstract

Aged rats recover poorly after unilateral stroke, whereas young rats recover readily possibly with the help from the contralateral, healthy hemisphere. In this study we asked whether anomalous, age-related changes in the transcriptional activity in the brains of aged rats could be one underlying factor contributing to reduced functional recovery. We analysed gene expression in the periinfarct and contralateral areas of 3-month- and 18-month-old Sprague Dawley rats. Our experimental end-points were cDNA arrays containing genes related to hypoxia signalling, DNA damage and apoptosis, cellular response to injury, axonal damage and re-growth, cell lineage differentiation, dendritogenesis and neurogenesis. The major transcriptional events observed were: (i) Early up-regulation of DNA damage and down-regulation of anti-apoptosis-related genes in the periinfarct region of aged rats after stroke; (ii) Impaired neurogenesis in the periinfarct area, especially in aged rats; (iii) Impaired neurogenesis in the contralateral (unlesioned) hemisphere of both young and aged rats at all times after stroke and (iv) Marked up-regulation, in aged rats, of genes associated with inflammation and scar formation. These results were confirmed with quantitative real-time PCR. We conclude that reduced transcriptional activity in the healthy, contralateral hemisphere of aged rats in conjunction with an early up-regulation of DNA damage-related genes and pro-apoptotic genes and down-regulation of axono- and neurogenesis in the periinfarct area are likely to account for poor neurorehabilitation after stroke in old rats.