Dataset Information

Proteomics Analysis of Brain Tissue in a Rat Model of Ischemic Stroke in the Acute Phase.

ABSTRACT: Background: Stroke is a leading health issue, with high morbidity and mortality rates worldwide. Of all strokes, approximately 80% of cases are ischemic stroke (IS). However, the underlying mechanisms of the occurrence of acute IS remain poorly understood because of heterogeneous and multiple factors. More potential biomarkers are urgently needed to reveal the deeper pathogenesis of IS. Methods: We identified potential biomarkers in rat brain tissues of IS using an iTRAQ labeling approach coupled with LC-MS/MS. Furthermore, bioinformatrics analyses including GO, KEGG, DAVID, and Cytoscape were used to present proteomic profiles and to explore the disease mechanisms. Additionally, Western blotting for target proteins was conducted for further verification. Results: We identified 4,578 proteins using the iTRAQ-based proteomics method. Of these proteins, 282 differentiated proteins, comprising 73 upregulated and 209 downregulated proteins, were observed. Further bioinformatics analysis suggested that the candidate proteins were mainly involved in energy liberation, intracellular protein transport, and synaptic plasticity regulation during the acute period. KEGG pathway enrichment analysis indicated a series of representative pathological pathways, including energy metabolite, long-term potentiation (LTP), and neurodegenerative disease-related pathways. Moreover, Western blotting confirmed the associated candidate proteins, which refer to oxidative responses and synaptic plasticity. Conclusions: Our findings highlight the identification of candidate protein biomarkers and provide insight into the biological processes involved in acute IS.

SUBMITTER: Zheng F

PROVIDER: S-EPMC7057045 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Proteomics Analysis of Brain Tissue in a Rat Model of Ischemic Stroke in the Acute Phase.

Zheng Fei F Zhou Yan-Tao YT Zeng Yi-Fu YF Liu Tao T Yang Zhao-Yu ZY Tang Tao T Luo Jie-Kun JK Wang Yang Y

Frontiers in molecular neuroscience 20200227

<b>Background</b>: Stroke is a leading health issue, with high morbidity and mortality rates worldwide. Of all strokes, approximately 80% of cases are ischemic stroke (IS). However, the underlying mechanisms of the occurrence of acute IS remain poorly understood because of heterogeneous and multiple factors. More potential biomarkers are urgently needed to reveal the deeper pathogenesis of IS. <b>Methods</b>: We identified potential biomarkers in rat brain tissues of IS using an iTRAQ labeling a ...[more]

PMID: 32174813

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Project description:Background and purpose: Early recognition and management of post-stroke dysphagia (PSD) based on MRI may reduce the incidence of complications. Combining clinical symptoms with applications of MRI, we aimed to identify the risk factors of PSD, develop a prediction scale with high accuracy and map key dysphagia brain areas. Methods: A total of 275 acute ischemic stroke patients were enrolled in this study, and 113 (41.1%) patients were diagnosed with PSD. All patients underwent the water-swallowing test (WST) and volume-viscosity swallow test (V-VST) within first 24 h following admission to assess swallowing. Vascular factors were evaluated and MRI brain scans were obtained within 3 days after symptom onset for each participant admitted to the hospital. T-test, chi-squared test and Fisher's exact test were used to investigate the associations of various patient characteristics with dysphagia, and multivariable logistic regression models were used to construct a prediction scale. Scale accuracy was assessed using receiver operating characteristic (ROC) analysis. We extracted white matter hyperintensities for each patient as potential brain lesions. Voxel-based lesion-symptom mapping (VLSM) was used to identify key brain areas for dysphagia. Results: Risk factors related with PSD were older age, history of atrial fibrillation, higher fasting blood glucose, NIH stroke scale, TOAST classification, progressive stroke, middle cerebral artery lesion and anterior cerebral artery lesion. Three variables with most significant associations, including NIH stroke scale, TOAST classification and progressive stroke, combined with age and gender, were used to construct a dysphagia prediction scale with high accuracy (AUC = 0.86). VLSM identified left inferior parietal gyrus as a key brain region for PSD. Conclusion: Risk factors of PSD were identified and a predictive model of dysphagia was constructed intelligently and automatically. The left inferior parietal gyrus was identified as a key brain area for dysphagia, which provides a new symptom-based treatment target for early rehabilitation in the future.

Project description:BackgroundInflammation is integral to the pathophysiology of ischemic stroke and a prime target for the development of new stroke therapies. The aim of the present study is to seek out the regulatory mechanism of circCDC14A in neuroinflammatory injury in tMCAO mice.MethodsThe expression level of circCDC14A in peri-infarct cortex and plasma of mice were detected by qPCR. The localization of circCDC14A in peripheral blood cells and peri-infarct cortex of tMCAO mice were explored by in situ hybridization and immunofluorescence colocalization staining. Lentivirus were microinjected into lateral ventricular of brain or injected into tail vein to interfere with the expression of circCDC14A, thus their effects on behavior, morphology, and molecular biology of tMCAO mice were analyzed.ResultsThe expression of circCDC14A in plasma and peri-infarct cortex of tMCAO mice significantly increased, and circCDC14A was mainly localized in neutrophils peripherally while in astrocytes in peri-infarct cortex centrally. Tail vein injection of lentivirus to interfere with the expression of circCDC14A significantly reduced the infarct volume (P < 0.01) at 72 h after reperfusion and density of activated astrocytes in peri-infarct cortex at 3 days, 5 days and 7 days after tMCAO modeling (all P < 0.0001). Moreover, mNSS (P < 0.0001) and survival rate (P < 0.001) were significantly improved within 7 days in si-circCDC14A group compared to circCon group. Additionally, morphology analysis showed the volume and surface area of each activated astrocytes significantly decreased (P < 0.0001). Quantification analysis measured the percentage of N2 phenotype among infiltrated neutrophils in brain sections and found N2 ratio was significantly higher in si-circCDC14A group compared to circCon group (P < 0.001).ConclusionKnocking down the expression of circCDC14A in peripheral blood cells relieved astrocytes activation in peri-infarct cortex, thereby relieved brain damage in the acute phase of ischemic stroke.

Dataset Information

Proteomics Analysis of Brain Tissue in a Rat Model of Ischemic Stroke in the Acute Phase.

Publications

Proteomics Analysis of Brain Tissue in a Rat Model of Ischemic Stroke in the Acute Phase.

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