Project description:Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. By high-throughput sequencing of infarct and ischemic penumbra tissue from middle cerebral artery embolization (MCAO) mice, we identified the CircRNA expression was dramatically and selectively regulated in the penumbra tissues.
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:Many hospitals lack facilities for accurate diagnosis of acute ischemic stroke (AIS). Circular RNA (circRNA) is highly expressed in the brain and is closely associated with stroke. In this study, we examined whether the blood-borne circRNAs can be promising candidates as adjunctive diagnostic biomarkers and their pathophysiological roles after stroke. We profiled the blood circRNA expression in mice subjected to experimental focal cerebral ischemia, and validated the selected circRNAs in AIS patients. We demonstrated that 128, 198 and 789 circRNAs were significantly altered at 5 min, 3 h and 24 h after ischemic stroke, respectively.
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: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:In order to explore the epigenetic characteristics of hemorrhagic transformation(HT) after acute ischemic stroke, we used transcriptome sequencing technology to analyze the global transcriptome expression profile of patients with and without HT after acute ischemic stroke and to study the differential expression of messenger RNA (mRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) between HT group and non-HT group.
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: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.
Project description:Circular RNAs (circRNAs) are a recently discovered non-coding RNA isoform capable of regulating neurological disease incidence. The present study was designed to characterize the circRNA expression profiles present in large-artery atherosclerosis (LAA)-type acute ischemic stroke patients. Using a RNA-seq approach, we characterized circRNA expression profiles in 5 LAA-stroke patients and 4 controls. We identified 182 and 176 circRNAs that were up- and down-regulated, respectively, in LAA-stroke patients relative to controls. Enrichment analyses suggested these differentially expressed circRNAs to primarily be associated with chromatin modification, autophagy, platelet activation, and neural precursor cell proliferation.