Multiple Mechanistic Models Reveal the Neuroprotective Effect of Ginkgo Bilobalides for the Treatment of Ischaemic Stroke
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE183546 | GEO | 2024/09/06
REPOSITORIES: GEO
Similar Datasets
Project description:Multiple Mechanistic Models Reveal the Neuroprotective Effect of Ginkgo Bilobalides for the Treatment of Ischaemic Stroke
| PRJNA761275 | ENA
Project description:Glucagon-like Peptide-1 receptor agonists (GLP-1RA) are gaining increasing momentum as possible neuroprotective agents in acute ischemic stroke. In this study, we investigate the neuroprotective effects of a novel GLP-1RA, Semaglutide, in the treatment of acute ischemic stroke and their underlying mechanisms. The current study first mapped comprehensive proteomic changes after acute ischemic stroke treated with Semaglutide, providing a foundation for developing potentially therapeutic targets for anti-acute ischemic stroke and clinically prognostic biomarkers of stroke.
2024-05-08 | PXD052130 |
Project description:Cardiac myxoma (CM) is an important aetiology of stroke in young adults, and its diagnosis is difficult in patients having stroke because of the lack of diagnostic biomarkers. Tumour-derived exosomes play a crucial role in tumour growth, metastasis, and immune regulation, and monitor disease development. We established an RNA-sequencing dataset for long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in the plasma and tumour-derived exosomes from four patients with cardiac myxoma-related ischaemic stroke (CM-IS) and six patients with cardiac myxoma without ischaemic stroke (non-IS CM). Clean data (15.48 Gb) were obtained for lncRNAs and mRNAs. Moreover, 5,533 lncRNAs, 1,331 known miRNAs, and 412 new miRNAs were identified. Finally, gene expression profiles and differentially expressed genes were analysed in 20 samples. In the plasma samples, 74 miRNAs, 12 lncRNAs, and 693 mRNAs were identified. Tumour-derived tissue samples contained 61 miRNAs, 67 lncRNAs, and 433 mRNAs. This dataset provides a significant resource for relevant researchers to explore the potential dysregulated lncRNAs, miRNAs, and mRNAs of plasma and tumour-derived exosomes in CM-IS versus CM without stroke.
2024-10-25 | GSE272079 | GEO
Project description:Cardiac myxoma (CM) is an important aetiology of stroke in young adults, and its diagnosis is difficult in patients having stroke because of the lack of diagnostic biomarkers. Tumour-derived exosomes play a crucial role in tumour growth, metastasis, and immune regulation, and monitor disease development. We established an RNA-sequencing dataset for long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in the plasma and tumour-derived exosomes from four patients with cardiac myxoma-related ischaemic stroke (CM-IS) and six patients with cardiac myxoma without ischaemic stroke (non-IS CM). Clean data (15.48 Gb) were obtained for lncRNAs and mRNAs. Moreover, 5,533 lncRNAs, 1,331 known miRNAs, and 412 new miRNAs were identified. Finally, gene expression profiles and differentially expressed genes were analysed in 20 samples. In the plasma samples, 74 miRNAs, 12 lncRNAs, and 693 mRNAs were identified. Tumour-derived tissue samples contained 61 miRNAs, 67 lncRNAs, and 433 mRNAs. This dataset provides a significant resource for relevant researchers to explore the potential dysregulated lncRNAs, miRNAs, and mRNAs of plasma and tumour-derived exosomes in CM-IS versus CM without stroke.
2024-10-25 | GSE272078 | GEO
Project description:A neuroprotective locus modulates ischemic stroke infarction independent of collateral vessel anatomy
| PRJNA707067 | ENA
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: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:Although Wnt signaling is critical for blood-brain barrier function, neuronal survival and adult neurogenesis, Wnt proteins are poorly suited as therapeutics for stroke given production and pharmacokinetic challenges. Here, we show that R-spondins (RSPOs), a family of easily produced secreted proteins that robustly augment Wnt signaling, were widely expressed in adult mouse brain and upregulated upon ischemia and reperfusion injury. Neutralizing endogenous RSPOs with their membrane receptor LGR5 and ZNRF3/RNF43 soluble ectodomains increased cerebral infarction in a murine stroke model. Conversely, systemic administration of RSPOs substantially reduced cerebral infarction and improved neurological outcomes. The neuroprotective effects of RSPOs were dependent on LGR4/ZNRF3-mediated canonical Wnt/-catenin signaling in the endothelia, neuronal cells and neural stem/progenitor cells, all of which contributed synergistically to reduce cerebral ischemia/reperfusion injury. Thus, we identified a previously unknown neuroprotective mechanism and the therapeutic potential of recombinant RSPOs in ischemic stroke.
2023-10-07 | GSE159453 | GEO
Project description:Wnt signaling is critical for blood-brain barrier function, neuronal survival and adult neurogenesis, yet Wnt proteins are poorly suited as therapeutics for stroke due to production and pharmacokinetic challenges. Here, we show that R-spondins (RSPOs), a family of easily produced and secreted proteins capable of robustly augmenting Wnt signaling, are widely expressed in adult mouse brain and upregulated upon ischemia and reperfusion injury. Neutralizing endogenous RSPOs with the soluble ectodomains of their membrane receptors LGR5, ZNRF3 and RNF43 increased cerebral infarction in a murine stroke model. Conversely, systemic administration of RSPOs substantially reduced cerebral infarction and improved neurological outcomes. The neuroprotective effects of RSPOs were dependent on LGR4/ZNRF3-mediated augmentation of canonical Wnt/-catenin signaling in endothelial and neuronal cells, which in turn promoted blood-brain barrier integrity, neuronal PDGF-CC expression and survival. Further, RSPOs promotes the proliferation and expansion of neural stem/progenitor cells and post-stroke neurogenesis. Thus, we identify a previously unknown neuroprotective and pro-neurogenic mechanism and describe the therapeutic potential of recombinant RSPOs in ischemic stroke.
2023-10-07 | GSE159454 | GEO
Project description:Astrogliosis is a hallmark of the response to brain ischemia, comprised of changes in gene expression and morphology. Hsp72 protects from cerebral ischemia, and although several mechanisms of protection have been investigated, effects on astrocyte activation are unknown. To identify potential mechanisms of protection, gene expression was assessed in mice subjected to middle cerebral artery (MCAO) or sham surgery, of either wildtype (WT) or Hsp72-overexpressing (Hsp72Tg) mice. After stroke, both genotypes exhibited genes related to cell death, stress response, and immune response. Furthermore, genes indicative of astrocyte activation, including cytoskeletal proteins and cytokines, were upregulated. To measure astrocyte activation after stroke, detailed histological and morphological analyses were performed in the cortical penumbra after stroke using unbiased stereology. Consistent with other reports, we observed a marked and persistent increase in glial fibrillary acidic protein (GFAP ) as soon as 3 hours after MCAO. In contrast, vimentin immunoreactivity appeared 12-24 hours after stroke, peaked at 72 hours, and returned to baseline after 30 days. Surprisingly, no change in overall astrocyte number was observed based on glutamine synthetase (GS) immunoreactivity. To determine if Hsp72Tg mice exhibited altered astrocyte activation compared to WT controls, morphological evaluation by fractal analysis was used. Overexpression of Hsp72 reduced astrocyte cell area, arbor area, and to a lesser extent fractal dimension, 72 hours following stroke. In conclusion, in vivo overexpression of Hsp72 alters gene expression following stroke, including genes involved in astrocyte activation, and decreases astrocyte activation acutely following MCAO. Thus, modulation of astrogliosis may be a neuroprotective mechanism exerted by Hsp72 after ischemia. A total of 10 samples were analyzed, with 5 of each genotype, wildtype (WT) and Hsp72-overexpressing (Hsp72Tg) mice. Of the 5 in each group, 3 received middle cerebral artery occlusion (MCAO) and 2 received a sham surgery. The sham samples serve as the controls for the MCAO samples in each genotype. All samples were taken from the ischemic or control hemisphere 24 hours after surgery.
2013-01-11 | E-GEOD-28731 | biostudies-arrayexpress