Genomics of the periinfarction cortex after focal cerebral ischemia

Aigang Lu, Yang Tang, Ruiqiong Ran, Joseph F. Clark, Bruce J. Aronow, Frank R Sharp

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

Understanding transcriptional changes in brain after ischemia may provide therapeutic targets for treating stroke and promoting recovery. To study these changes on a genomic scale, oligonucleotide arrays were used to assess RNA samples from periinfarction cortex of adult Sprague-Dawley rats 24 h after permanent middle cerebral artery occlusions. Of the 328 regulated transcripts in ischemia compared with sham-operated animals, 264 were upregulated, 64 were downregulated, and 163 (49.7%) had not been reported in stroke. Of the functional groups modulated by ischemia: G-protein-related genes were the least reported; and cytokines, chemokines, stress proteins, and cell adhesion and immune molecules were the most highly expressed. Quantitative reverse transcription polymerase chain reaction of 20 selected genes at 2, 4, and 24 h after ischemia showed early upregulated genes (2 h) including Narp, Rad, G33A, HYCP2, Pim-3, Cpg21, JAK2, CELF, Tenascin, and DAF. Late upregulated genes (24 h) included Cathepsin C, Cip-26, Cystatin B, PHAS-I, TBFII, Spr, PRG1, and LPS-binding protein. Glycerol 3-phosphate dehydrogenase, which is involved in mitochondrial reoxidation of glycolysis derived NADH, was regulated more than 60-fold. Plasticity-related transcripts were regulated, including Narp, agrin, and Cpg21. A newly reported lung pathway was also regulated in ischemic brain: C/EBP induction of Egr-1 (NGFI-A) with downstream induction of PAI-I, VEGF, ICAM, ILI, and MIPI. Genes regulated acutely after stroke may modulate cell survival and death; also, late regulated genes may be related to tissue repair and functional recovery.

Original languageEnglish (US)
Pages (from-to)786-810
Number of pages25
JournalJournal of Cerebral Blood Flow and Metabolism
Volume23
Issue number7
StatePublished - Jul 1 2003
Externally publishedYes

Keywords

  • Cathepsins
  • Cerebral ischemia
  • DNA microarrays
  • Egr-1
  • Functional genomics
  • Gene expression
  • Glycerol 3-phosphate dehydrogenase

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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