on January 3, 2005
Published online before print January 3, 2005, doi: 10.1161/01.CIR.0000152105.79665.C6
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Submitted on May 26, 2004
From the Section of Neurology, University of Manitoba, Winnipeg, Manitoba, Canada (D.F.M.); Stroke Neuroscience Unit (H.L., V.W., H.Y., A.E.B.), Biostatistics Branch (N.J.), Micro-Array Core Facility (R.A.C., A.E.), Neuroimmunology Branch (G.B.), and Developmental and Metabolic Neurology Branch (E.G.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md; Laboratory of Cellular Hematology, CBER, FDA, Rockville, Md (M.P.G.); and Cell and Cancer Biology Branch, National Cancer Institute, NIH, Bethesda, Md (E.Z.). * To whom correspondence should be addressed. E-mail: bairda{at}ninds.nih.gov.
Background--Direct brain biopsy is rarely indicated during acute stroke. This study uses peripheral blood mononuclear cells (PBMCs) to determine whether a systemic gene expression profile could be demonstrated in patients with acute ischemic stroke. Methods and Results--Using oligonucleotide microarrays, we compared the gene expression profile of an index cohort of 20 patients with confirmed ischemic stroke on neuroimaging studies with that of 20 referent subjects. Validation studies used quantitative real-time polymerase chain reaction to measure the levels of 9 upregulated genes in the index cohort, and an independent cohort of 9 patients and 10 referent subjects was prospectively studied to determine the accuracy of the Prediction Analysis for Microarrays list to classify stroke. After correction for multiple comparisons with the Bonferroni technique, 190 genes were significantly different between the stroke and referent groups. Broad classes of genes included white blood cell activation and differentiation ( Conclusions--This study demonstrated an altered gene expression profile in PBMCs during acute ischemic stroke. Some genes with altered expression were consistent with an adaptive response to central nervous system ischemia.
Revised on September 11, 2004
Accepted on October 20, 2004
Using Peripheral Blood Mononuclear Cells to Determine a Gene Expression Profile of Acute Ischemic Stroke. A Pilot Investigation
David F. Moore MD, PhD, DIC,
60%), genes associated with hypoxia and vascular repair, and genes potentially associated with an altered cerebral microenvironment. Real-time polymerase chain reaction confirmed increased mRNA expression in 9 of 9 upregulated stroke-associated genes in the index cohort. A panel of 22 genes derived from the Prediction Analysis for Microarrays algorithm in the index cohort classified stroke in the validation cohort with a sensitivity of 78% and a specificity of 80%. Control for the Framingham stroke risk score revealed only a partial dependence of the stroke gene expression profile in PBMCs on vascular risk.
Key words: cerebral infarction • genes • ischemia • stroke
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