Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans

Frank R Sharp, Glen C. Jickling, Boryana Stamova, Yingfang Tian, Xinhua Zhan, Da Liu, Beth Kuczynski, Christopher D. Cox, Bradley Ander

Research output: Contribution to journalReview article

52 Scopus citations

Abstract

Whole genome expression microarrays can be used to study gene expression in blood, which comes in part from leukocytes, immature platelets, and red blood cells. Since these cells are important in the pathogenesis of stroke, RNA provides an index of these cellular responses to stroke. Our studies in rats have shown specific gene expression changes 24 hours after ischemic stroke, hemorrhage, status epilepticus, hypoxia, hypoglycemia, global ischemia, and following brief focal ischemia that simulated transient ischemic attacks in humans. Human studies show gene expression changes following ischemic stroke. These gene profiles predict a second cohort with 90% sensitivity and specificity. Gene profiles for ischemic stroke caused by large-vessel atherosclerosis and cardioembolism have been described that predict a second cohort with 85% sensitivity and specificity. Atherosclerotic genes were associated with clotting, platelets, and monocytes, and cardioembolic genes were associated with inflammation, infection, and neutrophils. These gene profiles predicted the cause of stroke in 58% of cryptogenic patients. These studies will provide diagnostic, prognostic, and therapeutic markers, and will advance our understanding of stroke in humans. New techniques to measure all coding and noncoding RNAs along with alternatively spliced transcripts will markedly advance molecular studies of human stroke.

Original languageEnglish (US)
Pages (from-to)1513-1531
Number of pages19
JournalJournal of Cerebral Blood Flow and Metabolism
Volume31
Issue number7
DOIs
StatePublished - 2011

Keywords

  • brain
  • gene expression profiling
  • ischemia
  • microarrays

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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