Publications (2)6.85 Total impact
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Article: Microarray analysis of the global gene expression profile following hypothermia and transient focal cerebral ischemia.
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ABSTRACT: Hypothermia is one of the most robust experimental neuroprotective interventions against cerebral ischemia. Identification of molecular pathways and gene networks together with single genes or gene families that are significantly associated with neuroprotection might help unravel the mechanisms of therapeutic hypothermia. We performed a microarray analysis of ischemic rat brains that underwent 90 min of middle cerebral artery occlusion (MCAO) and 48 h of reperfusion. Hypothermia was induced for 4 h, starting 1 h after MCAO in male Wistar rats. At 48 h, magnetic resonance imaging (MRI) was performed for infarct volumetry, and functional outcome was determined by a neuroscore. The brain gene expression profile of sham (S), ischemia (I), and ischemia plus hypothermia (HI) treatment were compared by analyzing changes of individual genes, pathways, and networks. Real-time reverse-transcribed polymerase chain reaction (RT-PCR) was performed on selected genes to validate the data. Rats treated with HI had significantly reduced infarct volumes and improved neuroscores at 48 h compared with I. Of 4067 genes present on the array chip, HI compared with I upregulated 50 (1.23%) genes and downregulated 103 (3.20%) genes equal or greater than twofold. New genes potentially mediating neuroprotection by hypothermia were HNRNPAB, HIG-1, and JAK3. On the pathway level, HI globally suppressed the ischemia-driven gene response. Twelve gene networks were identified to be significantly altered by HI compared with I. The most significantly altered network contained genes participating in apoptosis suppression. Our data suggest that although hypothermia at the pathway level restored gene expression to sham levels, it selectively regulated the expression of several genes implicated in protein synthesis and folding, calcium homeostasis, cellular and synaptic integrity, inflammation, cell death, and apoptosis.Neuroscience 02/2012; 208:109-22. · 3.38 Impact Factor -
Article: Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke.
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ABSTRACT: 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. 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). 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. 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.Journal of Neurology 06/2008; 255(5):723-31. · 3.47 Impact Factor
