Enhanced HRG production following rt-PA treatment modulate neutrophil immune activity and hemorrhagic transformation in ischemic stroke
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PROVIDER: PRJNA1037553 | ENA |
REPOSITORIES: ENA
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Project description:Intravenous thrombolysis (IVT) with recombinate tissue plasminogen activatior (rt-PA) remains the primary approach for the treatment of acute ischemic stroke (AIS). Based on the short half-life of rt-PA, it is speculated that the coagulative/fibrinolytic cascade induced by alteplase administration might have subsequent longer effect on immune modulation. The exact role of Histidine-rich glycoprotein (HRG), which was found elevated following thrombolysis in this study, on affecting the innate immunity and hemorrhagic transformation (HT) following thrombolysis was investigated in this study. RNA sequencing was performed to show different expressed genes under HRG treatment and revealing the potential regulating pathway.
2024-07-13 | GSE247434 | GEO
Project description:In this study, a total of 10 patients who received rt-PA were enrolled. Plasma samples were collected before and 1 hour after the rt-PA infusion for proteomic analysis. Blood sample collection has been approved by Tianjin Medical University General Hospital Ethics Committee, and collection was conducted according to the Declaration of Helsinki. Informed consent was obtained from all participants, and all experiments were conducted in accordance with Chinese laws and institutional guidelines.
2024-07-12 | PXD046676 | Pride
Project description:In this study, a total of 10 patients who received rt-PA were enrolled. Plasma samples were collected before and 1 hour after the rt-PA infusion for proteomic analysis. Blood sample collection has been approved by Tianjin Medical University General Hospital Ethics Committee, and collection was conducted according to the Declaration of Helsinki. Informed consent was obtained from all participants, and all experiments were conducted in accordance with Chinese laws and institutional guidelines.
2024-07-12 | PXD046738 | Pride
Project description:Objective:To investigate the feasibility and safety of remote ischemic postconditioning (RIPC) in acute ischemic stroke patients after intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis (IVT). Methods:We performed a pilot randomized trial involving acute ischemic stroke patients with IVT. The patients were randomized 1:1 to receive RIPC or standard medical therapy. In the RIPC group, the participants underwent instant RIPC within 2 h of IVT, followed by repeated RIPC therapy for 7 days. The feasibility end point was the completion of RIPC and time from the first RIPC to finishing IVT in the RIPC group. The safety end point included tissue and neurovascular injury resulting from RIPC, changes in vital signs, level of plasma myoglobin, any hemorrhagic transformation, and other adverse events. Results:Thirty patients (15 RIPC and 15 Control) were recruited after IVT. The mean age was 65.7 ± 10.2 years, with a National Institutes of Health Stroke Scale (NIHSS) score of 6.5 (4.0-10.0). The completion rate for RIPC was 97.0%. The mean time from first RIPC to completing IVT was 66.0 (25.0-75.0) min in the RIPC group. One case of hemorrhagic transformation was observed in the RIPC group. No significant difference was found in the level of myoglobin between the two groups (P > 0.05). Interpretation:RIPC is effective and safe for AIS patients after intravenous rt-PA thrombolysis.
| S-EPMC6389851 | biostudies-literature
Project description:Cluster analysis using nonlinear dimensionality reduction ([tSNE]) revealed the differences in global gene expression profiles of healthy and injured striatum, and identified clusters of cells with unique genetic signatures in both ischemic brain and hemorrhagic brain. Genes with p-value < 0.05 and fold change ≥1.5 were regarded as differentially expressed genes (DEGs). For astrocytes, 135 DEGs were downregulated in hemorrhagic stroke compared to ischemic stroke. The secondary profiling of astrocytic subtypes yielded 10 different subtypes with distinct functional cell identities. For microglia, tSNE map indicated the distribution and proportion of microglia/macrophage were very similar in in the ischemic and hemorrhagic stroke models. We obtained 75 DEGs in total (hemorrhagic stroke vs. ischemic stroke, 54 were upregulated, 21 were downregulated) .
2021-10-31 | GSE167593 | GEO
Project description:In acute ischemic stroke, the only FDA-approved drug; recombinant tissue plasminogen activator (rt-PA) is limited by restricted time-window due to an enhanced risk of hemorrhagic transformation which is thought to be caused by metalloproteinase (MMP). In experimental stroke inhibitors of the mitogen-activated protein kinase kinase extracellular signal-regulated kinase kinase (MEK) 1/2 pathways reduce the MMPs. This study evaluated whether a MEK1/2 inhibitor in combination with rt-PA can prevent the detrimental effects of delayed rt-PA therapy in stroke. Thromboembolic stroke was induced in C57 black/6J mice and the MEK1/2 inhibitor U0126 was administrated 3.5 h and rt-PA 4 h post stroke-onset. Treatment with rt-PA demonstrated enhanced MMP-9 protein levels and hemorrhagic transformation which was prevented when U0126 was given in conjunction with rt-PA. By blocking the MMP-9 with U0126 the safety of rt-PA administration was improved and demonstrates a promising adjuvant strategy to reduce the harmful effects of delayed rt-PA treatment in acute ischemic stroke.
| S-EPMC8184783 | biostudies-literature
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.
2022-03-30 | GSE199435 | GEO
Project description:Background and purposeIschemic stroke lesion volumes have proven difficult to analyze due to the extremely skewed shape of their underlying distribution. We introduce an extension of generalized linear models, beta regression, as a possible method of modeling extremely skewed distributions as evidenced in ischemic stroke lesion volumes.MethodsThe NINDS rt-PA clinical trials measured ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion volumes from these trials were analyzed using beta regression. A multi-variable regression model associating explanatory variables with ischemic stroke lesion volumes was constructed using accepted model building strategies and compared with the previously published volumetric analysis.ResultsBeta regression produced a similar model when compared to the previous analysis published by the study group. All previously identified variables of importance were detected in the model building process. The age by treatment interaction described in previous studies was also found in this analysis, confirming the strong effect age has on stroke outcomes. Further, a treatment effect was elicited in terms of odds ratios, yielding a previously unknown quantification of the effect of rt-PA on lesion volumes.ConclusionsBeta regression proved adept in modeling ischemic stroke lesions and offered the interpretation of covariates in terms of odds ratios. Beta regression is seen as a legitimate alternative to analyze ischemic stroke volumes.
| S-EPMC3186717 | biostudies-literature
Project description:The proteome of cerebral thrombi from patients recanalized by mechanical thrombectomy in an acute phase of stroke was carried out to determine biomarkers of stroke radio-clinical outcomes for stroke physicians (clinical outcome and mortality at 3 months, intracranial hemorrhagic transformation, etc.). Proteome of cerebral thrombi was also used to elucidate stroke physiopathology (paradoxical effect of glucose in acute phase of stroke) and evaluate recanalization treatments (intravenous thrombolysis by rt-PA and/or thrombectomy efficiency). ThrombiOMIC database was incremented by proteomic analyses of cerebral thrombi successfully retrieved from all consecutive stroke patients (n=59) with large vessel occlusion treated by mechanical thrombectomy in acute phase between October 2018 and August 2019 in the intensive care stroke unit of the University Hospital of Nice (France).
2024-01-28 | PXD048837 | Pride
Project description:IntroductionThe neutrophil-to-lymphocyte ratio (NLR) has been shown to be a marker associated with inflammation and is independently associated with the adverse clinical outcomes of symptomatic intracranial hemorrhage, cancer, and cardiovascular disease. Hemorrhagic transformation (HT) is a serious complication of ischemic cerebral infarction and can be intensified by therapeutic interventions for acute ischemic stroke (AIS). The purpose of our research was to explore the predictive effect of NLR for HT in patients with AIS and to determine the best predictive value.MethodsPubMed, Web of Science, EMBASE, MEDLINE, Cochrane, and Google Scholar were searched. The primary endpoint was HT, and subgroup analysis was performed. Review Manager software version 5.3 was used to statistically analyze the outcomes.ResultsA total of seven studies including 3,726 patients met the inclusion criteria. The pooled odds ratio (OR) value of the high NLR that predicted HT in AIS patients was 1.53 (95% CI, 1.21-1.92; p = .0003). In addition, 1.10 (95% CI, 1.05-1.15; p < .0001) was the pooled OR of the high NLR associated with increased 3-month mortality in patients with AIS. In the subgroup analysis with an NLR cutoff value of 7.5-11, the correlation between NLR above the cutoff value and the rate of HT in patients with AIS was statistically significant (OR, 7.93; 95% CI, 2.25-27.95; p = .001).ConclusionA high NLR can predict HT and 3-month mortality in patients with AIS. Regardless of the country of origin and the sampling time, an NLR with a cutoff value of 7.5-11 was independently associated with HT in AIS patients.
| S-EPMC6749596 | biostudies-literature