Ontology highlight
ABSTRACT:
PROVIDER: PRJNA686830 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13285660_1.fastq.gz | Fastqsanger.gz | |||
| SRR13285660_2.fastq.gz | Fastqsanger.gz | |||
| SRR13285661_1.fastq.gz | Fastqsanger.gz | |||
| SRR13285661_2.fastq.gz | Fastqsanger.gz | |||
| SRR13285662_1.fastq.gz | Fastqsanger.gz |
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Project description:Stroke is a kind of cerebrovascular disease with high mortality. TMAO has been shown to aggravate stroke outcomes, but its mechanism remains unclear. Mice were treated with TMAO in normal saline by oral gavage for 14 consecutive days. Then, mice were made into MCAO models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were assessed. Since microglia played a crucial role in stroke, microglia of MCAO mice were isolated for high-throughput sequencing to identify the most differentially expressed gene following TMAO treatment. Afterward, the downstream pathways of TMAO were investigated using primary microglia. Our results demonstrated that TMAO promoted the release of inflammatory cytokines in the brain of MCAO mice and promoted the activation of OGD/R microglial inflammasome, thereby exacerbating stroke outcomes. FTO/IGF2BP2 inhibited NLRP3 inflammasome activation in OGD/R microglia by downregulating the m6A level of NLRP3, TMAO can inhibit the expression of FTO and IGF2BP2, thus promoting the activation of NLRP3 inflammasome in OGD/R microglia. In conclusion, these results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in stroke through FTO/IGF2BP2.
2023-09-06 | GSE216349 | 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
Project description:Prenatal alcohol exposure (PAE) is linked to elevated risk for systemic adult-onset diseases like hypertension, impaired glucose and immune regulation, and in animal models, to impaired recovery from acute onset diseases like cerebrovascular ischemic stroke. Recent evidence suggests that the gastrointestinal system rapidly becomes dysbiotic following cerebrovascular stroke, resulting in systemic inflammation. We hypothesized that a history of PAE would modify the systemic effects of stroke, and transduce exposure-dependent transcriptomic changes in downstream sentinel tissues of the enteric portal circulation that have previously been linked to biobehavioral outcomes in rodent PAE models. Pregnant Sprague Dawley rats were exposed to repeated episodes of vaporized ethanol or room air from gestational day 8 to 19. At 5 months, progeny from each treatment condition were subjected to unilateral endothelin-1 induced occlusion of the middle cerebral artery and outcomes evaluated after 2 days while other progeny stayed stroke-naïve. Stroke induced disabilities were assessed by behavioral assays (adhesive removal, Vibrissae evoked fore-limb placement, circling) and infarct size. The mesenteric adipose tissue and liver transcriptomes were assessed by sequencing, from age-matched stroke-exposed and stroke-naïve offspring. In stroke-naïve animals, pathway analysis identified rRNA processing as downregulated and citric acid cycle as upregulated in mesenteric adipose. Weighted gene correlation network analysis (WGCNA) identified, in the liver of stoke-naïve animals, a moderate but significant correlation between PAE status and necroptosis, a proinflammatory form of programmed cell death (Pearson’s r=0.554, p<0.05). Two days after a stroke, PAE rats exhibited worse neurological scores compared to controls (p<0.05). WGCNA after stroke identified an adipose gene network associated with B cell differentiation and NF-kappa B signaling as moderately correlated with post-stroke neurological function (Pearson's r=0.52, p=0.05). Post-stroke WGCNA also identified a liver proinflammatory gene network strongly correlated with post-stroke neurological function (Pearson's r=-0.63, p<0.01). PAE persistently alters the transcriptome of afferent tissue targets of enteric circulation in adult rat offspring. Moreover, PAE-linked enteric inflammation is correlated to worse outcomes following cerebrovascular ischemic stroke in adulthood. Enteric disturbances may mediate adverse brain health outcomes due to PAE in adulthood.
2023-08-29 | GSE217173 | GEO
Project description:Neutrophils, key players in the innate immune system, become activated following ischemic stroke. However, the influence of gut microbiota on neutrophil activation and its impact on inflammatory brain injury is not yet fully understood. In this study, we demonstrate that microbiota colonization in germ-free mice activates neutrophils and worsens disease outcomes. To investigate the phenotypic and molecular alterations in neutrophils, as well as their activity in stroke mice with either depleted or intact microbiota, we conducted a comparative proteomic analysis using liquid chromatography-based mass spectrometry. Our findings revealed that microbiota depletion leads to a downregulation of inflammatory proteins in circulating neutrophils and a reduction in neutrophil extracellular traps (NETs). A similar pattern was observed in neutrophils infiltrating the brain, accompanied by a decrease in infarct size and alleviated behavioral deficits.
2025-06-02 | PXD060229 | Pride
Project description:Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intra-cerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth, and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon ligation of the dCLN afferent lymphatics, and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke.
2024-02-27 | GSE252622 | GEO
Project description:Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development and maintenance and has therapeutic potential for treating neurological disorders. Herein, we investigated the effects of VEGF-C overexpression on brain fluid drainage and ischemic stroke outcomes in mice. Intra-cerebrospinal administration of an adeno-associated virus expressing mouse full-length VEGF-C (AAV-mVEGF-C) increased CSF drainage to the deep cervical lymph nodes (dCLNs) by enhancing lymphatic growth, and upregulated neuroprotective signaling pathways identified by single nuclei RNA sequencing of brain cells. In a mouse model of ischemic stroke, AAV-mVEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage, associated with mitigated microglia-mediated inflammation and increased BDNF signaling in brain cells. Neuroprotective effects of VEGF-C were lost upon ligation of the dCLN afferent lymphatics, and not mimicked by acute post-stroke VEGF-C injection. We conclude that VEGF-C prophylaxis promotes multiple vascular, immune, and neural responses that culminate in a protection against neurological damage in acute ischemic stroke.
2024-01-18 | GSE253051 | GEO
Project description:Ischemic stroke is a common acute CNS disorder leading to nearly half a million deaths per year in Europe. The high mortality is primarily owed to the limited treatment options of restoring blood flow in a narrow time window of several hours. Furthermore, inflammatory processes in the days and weeks after ischemic stroke contribute to tissue loss and neurological deficits. The key cells that influence and control this inflammatory cascade are microglia, the innate immune cells of the CNS. Microglia can be influenced and activated by e.g. lipopolysaccharide (LPS),a bacterial cell membrane component. It has been previously shown, that repetitive LPS stimuli prior to infarction (termed immunological preconditioning) lead to reduced infarct volumina in mouse models of ischemic stroke. Furthermore, our laboratory has shown, that phosphoinositide-3 kinase gamma mediates microglial functions after LPS-preconditioning. Hence, the aim of this work was to characterize proteomic alterations in microglia with (I) ischemic stroke in general in the tMCAO (transient middle cerebral artery occlusion) mouse model of ischemic stroke, (II) the influence of LPS-preconditioning on microglial proteomic alterations after tMCAO and (III) the role of PI3Ky in the microglial proteomic changes after tMCAO and preconditioning. This was done by a single LPS injection 3 days before tMCAO in wildtype mice and mice with PI3Ky knockout or knockin of the kinase dead form of PI3Ky.
2024-03-22 | PXD031930 | Pride
Project description:Ischemic stroke is a major threat to public health. Microglia-mediated neuroinflammation is a double-edged sword for neuronal survival after stroke. Triggering receptor expressed on myeloid cells 2 (Trem2) is specifically expressed on the surface of myeloid cell, including microglia. Here, we applied a photothrombotic mouse model of stroke to better understand the role of Trem2 in post-stroke neuroinflammation. In this model, Trem2 was sufficiently induced with sustainably elevated inflammatory responses. Our results demonstrated that Trem2-depletion can ameliorate ischemic injury with enhanced neuronal survival, reduced pro-inflammatory cytokine levels, and improved neurological functions. Our results suggested that Trem2 depletion is neuroprotective during ischemic stroke.
2024-12-29 | GSE280846 | GEO
Project description:Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post-cardiac arrest (CA) neurological injury. Here we analyzed circulating immune cells from a large OHCA patient cohort, finding that lymphopenia independently associated with poor neurological outcomes. Single cell RNA-sequencing of immune cells showed that T cells with features of both innate T cells and natural killer (NK) cells were increased in patients with favorable neurological outcomes. We more specifically identified an early increase in circulating diverse NKT cells (dNKT) in a separate cohort of OHCA patients with good neurological outcomes. These cells harbored a diverse T cell receptor repertoire but were consistently specific for sulfatide antigen. In mice, we found that sulfatide-specific dNKT cells trafficked to the brain after CA and resuscitation. In the brains of mice lacking NKT cells (Cd1d-/-), we observed increased inflammatory chemokine and cytokine expression and accumulation of macrophages when compared with wild-type mice. Cd1d-/- mice also had increased neuronal injury, neurological dysfunction, and worse mortality after CA. To therapeutically enhance dNKT cell activity, we treated mice with sulfatide lipid after CA, showing that it improved neurological function. Together, these data show that sulfatide-specific dNKT cells are associated with good neurological outcomes after clinical OHCA and are neuroprotective in mice after CA. Strategies to enhance the number or function of dNKT cells may thus represent a treatment approach for CA.
2025-01-30 | GSE280524 | GEO
Project description:Renin-angiotensin system (RAS) inhibition reduces stroke and improves brain capillary integrity in stroke prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis that treatment with an angiotensin II receptor subtype 1 (AT1R) antagonist has different effects, compared to an angiotensin converting enzyme (ACE) inhibitor, on gene expression in blood-brain barrier (BBB) capillaries. Six weeks old SHRSP were treated with either olmesartan (4 mg/kg, n=20), lisinopril (6 mg/kg , n=20) or remained untreated (n=20). Blood pressure was controlled by tail-cuff measurement. After 5 weeks the animals were sacrificed and cerebral capillaries were isolated. mRNA was extracted and analyzed with rat GeneChip DNA arrays. Additionally, brain histology and monocyte/macrophage infiltrates were determined. Both treatments similarly reduced neurological signs of stroke, stroke mortality, and monocyte/macrophage infiltration, compared to controls. Blood pressure was not influenced significantly by both drugs. We found 42 transcripts that were regulated by both treatments in the same manner. These genes were mostly related to inflammation. We also observed 39 differentially expressed genes between the two treatment groups that typically contribute to cell growth and differentiation. This study demonstrates that, despite similar effects on cerebral pathology and outcome, ACE inhibition and AT1R blockade have distinct molecular effects on gene expression in BBB capillaries.
2007-10-31 | E-GEOD-1548 | biostudies-arrayexpress