Project description:<p>The third leading cause of death in the United States, stroke is an acute neurological event leading to death of neural tissues.
Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are
hemorrhagic, resulting from bleeding into the brain. Stroke is a complex disorder and likely multigenic in nature, resulting from
a combination of genetic and environmental factors. These well characterized risk factors that contribute to the incidence of stroke
include hypertension, cardiac disease, sickle cell disease, hyperhomocysteinemia, family history of stroke and smoking.
</p>
<p>ISGS aim is to perform a prospective genetic association study of ischemic stroke focusing on the hemostatic system. ISGS
is a 5-center case-control study of first-ever ischemic stroke cases and concurrent controls individually matched for age,
sex and recruitment site.
</p>
<p>This data includes that from subjects both banked in the <a href="http://ccr.coriell.org/Sections/Collections/NINDS/?SsId=10">
NINDS repository</a> with biologicals publicly available, and those whose samples are not banked/not available.
</p>
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<li><a href="http://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?view_pdf&stacc=phs000102.v1.p1" target="_blank">Data Use Certification Requirements (DUC)</a></li>
<li><a href="http://view.ncbi.nlm.nih.gov/dbgap-controlled" target="_blank">Apply here for controlled access to individual level data</a></li>
<li><a href="GetPdf.cgi?id=phd000582" target="_blank">Participant Protection Policy FAQ</a></li>
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<p>This study utilized the <a href="./study.cgi?id=phs000005">NINDS Repository Cerebrovascular/Stroke Study</a>,
and <a href="./study.cgi?id=phs000004">neurologically normal controls</a> from the sample population which are banked in the National
Institute of Neurological Disorders and Stroke (NINDS Repository) collection for a first stage whole genome analysis.</p>
Project description:<p>The third leading cause of death in the United States, stroke is an acute neurological event leading to death of neural tissues.
Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are
hemorrhagic, resulting from bleeding into the brain. Stroke is a complex disorder and likely multigenic in nature, resulting from
a combination of genetic and environmental factors. These well characterized risk factors that contribute to the incidence of stroke
include hypertension, cardiac disease, sickle cell disease, hyperhomocysteinemia, family history of stroke and smoking.
</p>
<p>ISGS aim is to perform a prospective genetic association study of ischemic stroke focusing on the hemostatic system. ISGS
is a 5-center case-control study of first-ever ischemic stroke cases and concurrent controls individually matched for age,
sex and recruitment site.
</p>
<p>This data includes that from subjects both banked in the <a href="http://ccr.coriell.org/Sections/Collections/NINDS/?SsId=10">
NINDS repository</a> with biologicals publicly available, and those whose samples are not banked/not available.
</p>
<!-- <p><b>Important links to apply for individual-level data</b>
<ol>
<li><a href="http://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?view_pdf&stacc=phs000102.v1.p1" target="_blank">Data Use Certification Requirements (DUC)</a></li>
<li><a href="http://view.ncbi.nlm.nih.gov/dbgap-controlled" target="_blank">Apply here for controlled access to individual level data</a></li>
<li><a href="GetPdf.cgi?id=phd000582" target="_blank">Participant Protection Policy FAQ</a></li>
</ol>
</p> -->
<p>This study utilized the <a href="./study.cgi?id=phs000005">NINDS Repository Cerebrovascular/Stroke Study</a>,
and <a href="./study.cgi?id=phs000004">neurologically normal controls</a> from the sample population which are banked in the National
Institute of Neurological Disorders and Stroke (NINDS Repository) collection for a first stage whole genome analysis.</p>
Project description:Elevated plasma homocysteine is an independent risk factor for cardiovascular disease and stroke, however the etiology remains poorly understood. Elevated homocysteine is known to inhibit methyltransferases including DNA methyltransferases, but no methylome-wide analysis of elevated homocysteine has been reported. Peripheral blood genomic DNA methylation in 8 Singaporean-Chinese ischemic stroke patients (4 male, 4 female) with varying homocysteine titer and hypertensive status were profiled using methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq) on Illumina Genome Analyzer IIx. A methylome wide screen was undertaken for gender, total plasma homocysteine, hypertension and age. The data show considerable variability within the small cohort, including at genes which are related to one carbon metabolism and cardiovascular disease. Peripheral blood genomic DNA methylation in 8 Singaporean-Chinese ischemic stroke patients (4 male, 4 female) was profiled using methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq) on Illumina Genome Analyzer IIx. Methylation parrterns were correlated with homocysteine levels, lypertensive status, gender and age.
Project description:We performed a genome-wide methylation study in whole-blood DNA from 404 ischemic stroke patient cohort, distributed across 3 ischemic stroke subtypes: Large-artery atherosclerosis (n=132), Small-artery disease (n=141) and Cardio embolic (n=127) . Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites. We performed a genome-wide methylation study in whole-blood DNA from 185 ischemic stroke patient cohort. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites.
Project description:The purpose of this project was to elucidate gene expression in the peripheral whole blood of acute ischemic stroke patients to identify a panel of genes for the diagnosis of acute ischemic stroke. Peripheral blood samples were collected in Paxgene Blood RNA tubes from stroke patients who were >18 years of age with MRI diagnosed ischemic stroke and controls who were non-stroke neurologically healthy. The results suggest a panel of genes can be used to diagnose ischemic stroke, and provide information about the biological pathways involved in the response to acute ischemic stroke in humans. Total RNA extracted from whole blood in n=39 ischemic stroke patients compared to n=24 healthy control subjects.
Project description:Background: Ischemic stroke is a disease with high rate of death and disability worldwide. This study investigated key circRNAs related to ischemic stroke. Methods: Three ischemic stroke patients and three healthy individuals were included in the current study to obtain the circRNA expression profiles by RNA sequencing. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. Finally, the expression levels of selected circRNAs were validated with qRT-PCR. Results: A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. The qRT-PCR results were largely in keeping with our RNA-seq data. Conclusion: The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.
Project description:Dysregulated long non-coding RNAs (lncRNAs) have been shown to contribute to the pathogenesis of ischemic stroke. However, the potential role of lncRNAs in post-stroke microglial reactivation remains largely unknown. Here, we uncovered that lncRNA-U90926 was significantly increased in the microglia exposed to ischemia/reperfusion in vivo and in vitro. In addition, adenovirus associated virus (AAV)-mediated microglial U90926 silencing alleviated neurological deficits and reduced infarct volume in experimental stroke mice. Microglial U90926 knockdown could reduce the infiltration of neutrophils into ischemic lesion site, which might be attributed to the downregulation of C-X-C motif ligand 2 (CXCL2). Mechanistically, U90926 directly bound to malate dehydrogenase (MDH2) and competitively inhibited MDH2-mediated decay of CXCL2 mRNA. Taken together, our study demonstrated that microglial U90926 aggravated ischemic brain injury via facilitating neutrophil infiltration, suggesting that U90926 might be a potential biomarker and therapeutic target for ischemic stroke.
Project description:Analysis of astrocytic gene expression profiles after ischemic stroke. Stroke is a complicated disease caused by the interaction of multiple celltypes. Results provide new insights into the molecular mechanisms underlying astrocytic activation after ischemic stroke.
Project description:Analysis of microglial gene expression profiles after ischemic stroke. Stroke is a complicated disease caused by the interaction of multiple celltypes. Results provide new insights into the molecular mechanisms underlying microglial activation after ischemic stroke.