Microbial characteristics of High stroke risk group.
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PROVIDER: PRJEB29939 | ENA |
REPOSITORIES: ENA
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Project description:Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard. Microarray analysis in peripheral blood cells includes eight patients with AF and stroke and eight AF subjects without stroke
2016-04-01 | E-GEOD-66724 | biostudies-arrayexpress
Project description:Post-injury dysfunction of humoral immunity accounts for infections and poor outcome in cardiovascular diseases. Immunoglobulin A (IgA), the most abundant mucosal antibody is produced by plasma B cells in intestinal Peyer’s patches (PP) and lamina propria. Here, we show that stroke and myocardial ischemia (MI) patients had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid and macroscopic shrinkage of PP caused by substantial B cell loss. Stroke/MI triggered neutrophils to release neutrophil extracellular traps (NETs). Depletion of neutrophils, NET-degradation, or blockade of NET-release inhibited PP shrinkage and loss of B cells and IgA in stroke mice. Also, stroke and MI patients had higher amounts of circulating NETs, correlating with reduced IgA levels. Strikingly, stroke patients treated with DNase-I had reduced circulating NETs and stable IgA levels. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological IgA secretion and how this can be inhibited in patients.
2024-03-17 | GSE254410 | GEO
Project description:The serum miRNAs were correlated with predicted the incidence of stroke.
2019-05-31 | GSE117064 | GEO
Project description:Prospective cohort studies and meta-analyses examining the relationship between HDL-cholesterol (C) and stroke risk are discordant and question the value of HDL-C as a marker for stroke risk prediction. However, the relationship between other metrics of HDL, function and proteome, and stroke remain unexplored. We investigated changes in HDL protein composition and function -cholesterol efflux capacity (CEC)- after acute ischemic stroke, and their relationship to long-term functional and neuronal recovery after stroke. Plasma samples were collected from healthy controls (N = 35) and from stroke patients either 24 (early, N = 35) or 96 hours (late, N = 20) after stroke onset. ABCA1 mediated CEC was measured using murine macrophages. Stroke recovery was assessed at 3 months after stroke event using the Modified Rankin Scores (MRS) and the NIH Stroke Scale (NIHSS). Proteomic analysis of HDL by parallel reaction monitoring indicated a distinct time-dependent remodeling after stroke. 15 proteins were significantly altered following stroke, with 6 proteins significantly changing between 24 and 96 h post stroke. Inflammation-related proteins (SAA1, SAA2, PON1) were increased at both time points. Macrophage CEC, consistent with inflammatory remodeling of HDL proteome, was reduced by 50% (P<0.0001) in both early and late post-stroke samples compared to the controls. Changes in 6 post-stroke significantly correlated with stroke recovery scores (P<0.05). Further, the multiple linear regression model adjusting for baseline stroke severity confirmed that these proteins that predict the stroke recovery. Changes in HDL associated proteins within the first 96 hours post stroke could be used as markers to predict functional stroke recovery.
2021-01-24 | PXD015001 | panorama
Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke aging mice, but not in young adults.
2023-11-27 | GSE241528 | GEO
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.
2020-10-24 | GSE159903 | GEO
Project description:Heat stroke is a life-threatening condition characterized by loss of thermoregulation and severe elevation of core body temperature, which can cause organ failure and damage to the central nervous system. While no definitive test exists to measure heat stroke severity, immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear. In this study, we used a mouse model of classic heat stroke to test the effect of immune challenge on pathology. Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non-uniform in size, suggesting younger, more active platelets. Levels of D-dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases presenting with the highest level of organ damage markers D-dimer levels dropped, indicating potential fibrinolysis-resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up-regulated in kidneys of heat-challenged animals, and these increases correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself. We conclude that heat stroke-induced coagulopathy may be a driving mechanistic force in heat stroke pathology, especially when exacerbated by prior infection, and that coagulation markers may serve as an accessible biomarker for heat stroke severity and therapeutic strategies.
2020-05-15 | GSE129188 | GEO
Project description:TMT-coupled proteomic analysis was conducted on mouse brain cortex tissue from five time-points up to four weeks post-stroke in the DH-MCAO mouse model. Nearly-half of the detected proteome was altered following stroke, with <10% of changes at relatively large scales. Clustering on the changed proteome defined four distinct expression patterns characterized by temporal and quantitative changes in innate and adaptive immune response pathways, and cytoskeletal and neuronal remodeling. Further analysis on a subset of top-hits, which temporally responded to stroke with relatively large and sustained changes, revealed that they were highly correlated to different cortical cytokines, and thereby potential pharmacodynamic biomarker candidates for inflammation-targeting therapies. Closer examination of the top enriched neurophysiologic pathways identified 57 proteins potentially associated with post-stroke recovery. Altogether, our study generated a rich dataset with candidate proteins worthy of further validation as biomarkers and/or therapeutic targets for stroke.
2021-06-10 | PXD025077 | Pride
Project description:Background: Maternal high-fat diet (MHFD) has been shown to increase susceptibility to neurological disease in later offspring, but the underlying mechanism is not clear. Fibroblast growth factor 21 (FGF21) has been reported to have a neuroprotective effect in stroke, but its mechanism of action remains unknown. In this study, we investigated the mechanism of the effect of MHFD on stroke in offspring in adulthood and the mechanism by which FGF21 acts on stroke and restores neurological function. Methods: We performed transcriptome sequencing analysis on D21 neonatal rats. Bodyweight and blood indicators were recorded in the adult rats after MHFD. FGF21 was administered 7 h after photochemical modeling twice a day for three consecutive days. Results: We found numerous mRNA changes between the MHFD group and a normal maternal diet (MND) group at D21, including genes related to astrocyte and PI3K/Akt pathways. The body weight, blood glucose, and triglycerides of the MHFD offspring were higher, ischemic lesions were larger, the number of activated astrocytes was lower, and the neurological function score was worse than that of the MND group. After FGF21 administration, WB and qPCR analyses showed that astrocytes and the PI3K/Akt pathway were upregulated, while NF-κB and inflammatory cytokines expression were inhibited in stroke and peri-stroke regions. Conclusion: Taken together, we conclude that MHFD alters the characteristics of astrocytes and other transcriptome changes in their offspring, leading to a worse prognosis of stroke, while FGF21 plays a neuroprotective role by inhibiting NF-κB and inflammatory factors and activating the PI3K/Akt pathway and activating more astrocytes in the MND group than the MHFD group.
2021-12-17 | GSE189679 | GEO
Project description:Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worst neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor 1 receptor antagonists enables microglia depletion that is followed by microglia repopulation after interruption of the treatment, without any known harm to the mice. We used this strategy aiming to rejuvenate microglia function and ameliorate stroke outcome in aged mice. Cerebral ischemia/reperfusion induced strong innate immune responses in microglia highlighted by prominent type-I interferon signalling, together with cellular metabolic perturbances and lipid droplet biogenesis. Old age increased innate immune responses in microglia, which also showed more lipid droplets than microglia of young mice. Microglia renewal in old mice prevented the exaggerated type I interferon response observed in microglia after stroke, reduced the lipid droplet content, and improved the neurological outcome of stroke. This study shows that microglia renewal in old mice rejuvenates some features of old microglia and improves stroke outcome.
2022-11-29 | GSE196737 | GEO