Spatial and temporal gene expression differences in core and periinfarct areas in experimental stroke: a microarray analysis

PLoS One. 2012;7(12):e52121. doi: 10.1371/journal.pone.0052121. Epub 2012 Dec 17.

Abstract

Background: A large number of genes are regulated to promote brain repair following stroke. The thorough analysis of this process can help identify new markers and develop therapeutic strategies. This study analyzes gene expression following experimental stroke.

Methodology/principal findings: A microarray study of gene expression in the core, periinfarct and contralateral cortex was performed in adult Sprague-Dawley rats (n = 60) after 24 hours (acute phase) or 3 days (delayed stage) of permanent middle cerebral artery (MCA) occlusion. Independent qRT-PCR validation (n = 12) was performed for 22 of the genes. Functional data were evaluated by Ingenuity Pathway Analysis. The number of genes differentially expressed was 2,612 (24 h) and 5,717 (3 d) in the core; and 3,505 (24 h) and 1,686 (3 d) in the periinfarct area (logFC>|1|; adjP<0.05). Expression of many neurovascular unit development genes was altered at 24 h and 3 d including HES2, OLIG2, LINGO1 and NOGO-A; chemokines like CXCL1 and CXCL12, stress-response genes like HIF-1A, and trophic factors like BDNF or BMP4. Nearly half of the detected genes (43%) had not been associated with stroke previously.

Conclusions: This comprehensive study of gene regulation in the core and periinfarct areas at different times following permanent MCA occlusion provides new data that can be helpful in translational research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cluster Analysis
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Rats
  • Reproducibility of Results
  • Stroke / genetics*
  • Stroke / metabolism
  • Stroke / pathology
  • Time Factors
  • Transcription, Genetic
  • Transcriptome*

Associated data

  • GEO/GSE36010

Grants and funding

This work was supported by grants from PS09/01606 (Spanish Ministry of Science) and by RENEVAS (RD07/0026/2003 – Spanish Neurovascular Network), Carlos III Research Institute, Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.