Genome-wide gene expression analysis for induced ischemic tolerance and delayed neuronal death following transient global ischemia in rats

J Cereb Blood Flow Metab. 2004 Feb;24(2):212-23. doi: 10.1097/01.WCB.0000106012.33322.A2.

Abstract

Genome-wide gene expression analysis of the hippocampal CA1 region was conducted in a rat global ischemia model for delayed neuronal death and induced ischemic tolerance using an oligonucleotide-based DNA microarray containing 8,799 probes. The results showed that expression levels of 246 transcripts were increased and 213 were decreased following ischemia, corresponding to 5.1% of the represented probe sets. These changes were divided into seven expression clusters using hierarchical cluster analysis, each with distinct conditions and time-specific patterns. Ischemic tolerance was associated with transient up-regulation of transcription factors (c-Fos, JunB Egr-1, -2, -4, NGFI-B), Hsp70 and MAP kinase cascade-related genes (MKP-1), which are implicated cell survival. Delayed neuronal death exhibited complex long-lasting changes of expression, such as up-regulation of proapoptotic genes (GADD153, Smad2, Dral, Caspase-2 and -3) and down-regulation of genes implicated in survival signaling (MKK2, and PI4 kinase, DAG/PKC signaling pathways), suggesting an imbalance between death and survival signals. Our study provides a differential gene expression profile between delayed neuronal death and induced ischemic tolerance in a genome-wide analysis, and contributes to further understanding of the complex molecular pathophysiology in cerebral ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / physiopathology*
  • Cell Death*
  • Cluster Analysis
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Genome*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • In Situ Hybridization
  • Male
  • Neurons / physiology*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • RNA, Messenger