Inflammation and the emerging role of the toll-like receptor system in acute brain ischemia

Brenda J. Marsh, Susan L. Stevens, Brian Hunter, Mary P. Stenzel-Poore

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Background and Purpose-Systemic administration of cytosine-guanine (CpG) oligodeoxynucleotides provides neuroprotection against subsequent cerebral ischemic injury. We examined the genomic response of leukocytes and brain cells after ischemia in the context of CpG preconditioning. Methods-RNA was isolated from circulating leukocytes and ischemic cortex 3 and 24 hours after middle cerebral artery occlusion after CpG or saline pretreatment and subjected to microarray analysis. Genes uniquely upregulated in CpG-pretreated mice were examined for overrepresented transcriptional regulatory elements. Results-CpG preconditioning induced a novel response to middle cerebral artery occlusion within circulating leukocytes that was dominated by natural killer cell-associated genes and the GATA-3 transcriptional regulatory element. Preconditioning also caused a novel brain response to stroke that was dominated by Type I interferon, interferon-associated genes, and transcriptional regulatory elements. Conclusion-CpG preconditioning invokes novel leukocyte and brain responses to stroke. In this, CpG may be a unique preconditioning agent, coordinating peripheral and brain responses to protect against ischemic injury.

Original languageEnglish (US)
Pages (from-to)S34-S37
JournalStroke
Volume40
Issue number3 SUPPL. 1
DOIs
StatePublished - Mar 1 2009

Keywords

  • Hypoxia-ischemia
  • Inflammation
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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