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

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...

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Bibliographic Details
Published in:Journal of Cerebral Blood Flow & Metabolism 2011-07, Vol.31 (7), p.1513-1531
Main Authors: Sharp, Frank R, Jickling, Glen C, Stamova, Boryana, Tian, Yingfang, Zhan, Xinhua, Liu, DaZhi, Kuczynski, Beth, Cox, Christopher D, Ander, Bradley P
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Gene Expression Profiling - methods
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Humans
Medical sciences
Nervous system (semeiology, syndromes)
Neurology
Oligonucleotide Array Sequence Analysis - methods
Review
RNA - blood
RNA - genetics
Stroke - blood
Stroke - diagnosis
Stroke - genetics
Vascular diseases and vascular malformations of the nervous system
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Summary: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.
ISSN:0271-678X
1559-7016
DOI:10.1038/jcbfm.2011.45