ORIGINAL COMMUNICATION

Journal of Neurology

, Volume 255, Issue 5, pp 723-731

First online:

Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke

  • C.  Grond-GinsbachAffiliated withDept. of Neurology, University of Heidelberg Email author 
  • , M. HummelAffiliated withIBE, Medical School LMU
  • , T. WiestAffiliated withDept. of Neurology, University of Heidelberg
  • , S. HorstmannAffiliated withDept. of Neurology, University of Heidelberg
  • , K. PflegerAffiliated withDept. of Neurology, University of Heidelberg
  • , M. Hergenhahn†Affiliated withDept. of Genetic Alterations in Carcinogenesis, German Cancer Research Center
  • , M. HollsteinAffiliated withDept. of Genetic Alterations in Carcinogenesis, German Cancer Research Center
  • , U. MansmannAffiliated withIBE, Medical School LMU
  • , A. J. GrauAffiliated withDept. of Neurology, Klinikum der Stadt Ludwigshafen
    • , S. WagnerAffiliated withDept. of Neurology, University of Heidelberg

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Abstract

Background and purpose

Ischemic stroke provokes a systemic inflammatory response. The purpose of this study was to characterize this response on the gene expression level in circulating mononuclear leukocytes from acute ischemic stroke (AIS) patients.

Methods

RNA from peripheral blood mononuclear cells (PBMCs) of AIS patients (24 + 2 hours after onset of symptoms) was analyzed with Affymetrix U133A GeneChips using a pooled design. We compared the gene expression signature from AIS patients (n = 20), stroke survivors (n = 15), patients with acute traumatic brain injury (ATBI, n = 15) and healthy control subjects without vascular risk factors (n = 15).

Results

Expression levels of 9682 probe sets with present calls on each GeneChip were compared. Between AIS patients and stroke survivors or between AIS patients and ATBI patients there were no significant differences in expression values of single genes after correction for multiple testing. However, comparison of the PBMC expression profiles from AIS patients and healthy subjects revealed significantly different expression (p = 0.012) of a single probe set, specific for phosphodiesterase 4 D (PDE4D). In order to detect modest expression differences in multiple genes with a presumed cumulative effect we studied the gene expression of functional groups of genes by global statistical tests. Analysis of 11 gene groups revealed differential expression between AIS patients and healthy subjects for genes involved in the inflammatory response (GeneOntology GO:0006954). Genes encoding the N-formyl peptide receptor-like 1 (FPRL1), interleukin-1 receptor antagonist (IL1RN) and complement component 3a receptor 1 (C3AR1) contributed most to the observed difference.

Conclusions

This transcriptome analysis did not identify significant changes between circulating mononuclear cells from AIS patients 24 hours after stroke and closely matched stroke survivors. However, comparing AIS patients with healthy control subjects revealed measurable differences in PDE4D and in inflammatory response genes when considered as a set.

Key words

acute ischemic stroke acute traumatic brain injury gene expression blood