Project description:The current treatment options for ischemic stroke aim to achieve reperfusion but are time critical. Novel therapeutic approaches that can be given beyond the limited time window of 3 - 4.5 hours are still an unmet need to be addressed to improve stroke outcome. The lack of oxygen and glucose in the area of ischemic injury initiates a pathological cascade leading to blood-brain barrier (BBB) breakdown, inflammation and neuronal cell death, a process that may be intercepted to limit stroke progression. Pericytes located at the blood/brain interface are one of the first responders to hypoxia in stroke and therefore a potential target cell for early stroke interventions. Using single-cell RNA sequencing in a mouse model of permanent middle cerebral artery occlusion, we investigated the temporal differences in transcriptomic signatures in pericytes at 1, 12, and 24 hours after stroke compared to the contralateral hemisphere. Our results reveal a stroke-specific subcluster of pericytes that is present at 12 and 24 hours and characterized by the upregulation of genes mainly related to cytokine signalling and immune response. This study identifies temporal transcriptional changes in the acute phase of ischemic stroke that reflect the early response of pericytes to the ischemic insult and its secondary consequences and may constitute potential future therapeutic targets.
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: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.
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:The roles of mRNA and microRNA (miRNA) are widely known in many diseases including acute ischemic stroke. About 60 % of all human messenger RNAs (mRNAs) are regulated by microRNAs. Integration analysis using mRNA and miRNA are important to elucidate pathogenesis. But the contribution of mRNA and miRNA, especially miRNA targeted mRNA, related with severity of acute ischemic stroke is not remain understood. To clarify the pathway related with the severity of acute ischemic stroke, we examined mRNA and miRNA integration analysis targeted for acute ischemic stroke.
Project description:The roles of mRNA and microRNA (miRNA) are widely known in many diseases including acute ischemic stroke. About 60 % of all human messenger RNAs (mRNAs) are regulated by microRNAs. Integration analysis using mRNA and miRNA are important to elucidate pathogenesis. But the contribution of mRNA and miRNA, especially miRNA targeted mRNA, related with severity of acute ischemic stroke is not remain understood. To clarify the pathway related with the severity of acute ischemic stroke, we examined mRNA and miRNA integration analysis targeted for acute 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:Acute stroke, with ischemic stroke comprising 80% of all cerebrovascular incidents, has been recognized as one of the core problems in clinical medicine in need of prevention and treatment. Intravenous rtPA is the mainstay and the highest class evidence based method of acute ischemic stroke treatment, and is currently recommended 0-4.5 hours after stroke onset. In most patients decision on i.v. rtPA administration is striaghtforward, however the biggest concern is the symptomatic intracranial haemorrhage (sICH), which occurs in 3-7% of all treated patients, and is associated with worse 90-day functional outcome and higher disability than in those untreated. Finding a method of the powerful (highly specific and selective) identification of patients at highest risk of sICH, in order to increase the percentage of stroke patients safely treated with rtPA, is one of the most important challenges in stroke research. To address this problem we designed a major and complex project to identify blood, neuroimaging, and clinical biomarkers combined for prospective assessment of the risk of intracranial hemorrhage (ICH) after thrombolytic treatment of acute ischemic stroke. Herein, we reveal our general methodological approach with shortlisting of blood protein candidates selected with Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) that in the future might increase sensitivity and selectivity of the rtPA-associated sICH risk calculations.
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:Our study reveals that ischemic stroke can influence the expression of LncRNAs and mRNAs in the peripheral blood at both the acute and subacute stages