title: Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: a pilot investigation.
abstract: 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.
  
  
  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 (approximately 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.
  
  
  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.
authors.affiliation: Section of Neurology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: David F
authors.initials: DF
authors.lastname: Moore
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Neal
authors.initials: N
authors.lastname: Jeffries
authors.forename: Violet
authors.initials: V
authors.lastname: Wright
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Cooper
authors.forename: Abdel
authors.initials: A
authors.lastname: Elkahloun
authors.forename: Monique P
authors.initials: MP
authors.lastname: Gelderman
authors.forename: Enrique
authors.initials: E
authors.lastname: Zudaire
authors.forename: Gregg
authors.initials: G
authors.lastname: Blevins
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Ehud
authors.initials: E
authors.lastname: Goldin
authors.forename: Alison E
authors.initials: AE
authors.lastname: Baird
mesh_terms: D000208:Acute Disease; D000222:Adaptation, Physiological / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000097:blood* / Q000235:genetics; D015331:Cohort Studies; D003199:Computer Systems; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction