Expression profiles of perihematomal brain tissues of intracerebral hemorrhage (ICH) mice treated with or without TEPP-46
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205082 | GEO | 2023/09/15
REPOSITORIES: GEO
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Project description:Expression profiles of perihematomal brain tissues of intracerebral hemorrhage (ICH) mice treated with or without TEPP-46
| PRJNA843688 | ENA
Project description:Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. While there is substantial interest in post-ICH neuroinflammation and associated pathophysiological mechanisms, these processes remain poorly understood. To further advance our understanding, we performed RNA-seq in the peripheral blood of ICH patients to test the hypothesis that ICH would induce inflammatory biological pathways. 16,640 genes were identified and 216 were significant DEGs after ICH (FDR<0.1). IPA identified three canonical pathways as the most statistically significantly activated by ICH: colorectal cancer metastasis signaling (Z-score 3.00, P=1.71E-5), interleukin-8 (IL-8) signaling (3.00, 8.44E-5), and nuclear factor-kappa B (NF-kB) activation by viruses (2.55, 1.78E-4). Inflammatory mediators of particular relevance included IL-8, NF-kB, ERK 1/2, and the integrins β3, α2b, and β5. Conclusion: ICH induced peripheral blood gene expression at 72 to 96 hours compared with 0 to 24 hours from symptom onset. DEGs that were highly expressed in the significant biological pathways included those related to inflammation and activation of the immune response. Further research is needed to determine if these changes affect outcomes and may represent new therapeutic targets.
2019-04-21 | GSE125512 | GEO
Project description:We show that intracerebroventricular administration of recombinant human cerebral dopamine neurotrophic factor (rhCDNF) accelerates hemorrhagic lesion resolution, reduces peri-focal edema, and improves neurological outcomes in an animal model of collagenase-induced ICH. We demonstrate that CDNF acts on microglia/macrophages in the hemorrhagic striatum by promoting scavenger receptor expression, enhancing erythrophagocytosis and increasing anti-inflammatory mediators while suppressing the production of pro-inflammatory cytokines. Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain’s myeloid cells for the treatment of ICH.
2022-12-19 | GSE216547 | GEO
Project description:To investigate age-dependent transcriptomic changes between young or aged intracerebral hemorrhage mice, we established collagenase IV-induced intracerebral hemorrhage mice models. Intracerebral hemorrhage was induced by infusion of sterile collagenase IV in ipsilateral caudate putamen of brain. We then performed gene expression profiling analysis using data obtained from RNA-seq of brain perihematomal tissues from young or aged ICH mice 24 hours after intracerebral hemorrhage.
2022-04-29 | GSE200575 | GEO
Project description:Secondary injury causes death and dependence after spontaneous intracerebral haemorrhage (ICH). Having found that ICH is associated with activation of genes regulated by the transcription factor NRF2, we performed bulk RNA sequencing of perihaematomal and anatomically matched contralateral brain homogenate obtained at autopsy from a cohort of patients who died either within 24h of ICH or between 4-14 days of ICH onset, to investigate the spatiotemporal evolution of this Nrf2 activation.
2024-08-13 | E-MTAB-14323 | biostudies-arrayexpress
Project description:Introduction: Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. microRNA (miRNA) are short, noncoding nucleic acids that are critical regulators gene expression and promising novel therapeutic targets. Our prior research of mRNA-seq in swine demonstrated that ICH increased inflammatory gene expression within six hours of onset. We now present findings from an integrated analysis of miRNA-seq and mRNA-seq in peripheral blood mononuclear cells (PBMCs) from swine ICH. We tested the hypothesis that ICH would induce miRNA within six hours and that differentially expressed (DE) inflammatory genes would be targets of the DE miRNA. Methods: In 10 pigs, one PBMC sample was collected immediately prior to ICH induction and a second six hours later; miRNA-seq and mRNA-seq were performed. To determine the miRNA that primarily regulated the DE mRNA, an aggregate score was calculated for each miRNA of interest that incorporated the combined summary statistics of its DE target mRNA. Networks of molecular interactions were generated for the target mRNA and the combined miRNA/target mRNA. Results: A total of 227 miRNA were identified with alignment to the Sus scrofa (swine) genome, and 46 were DE (FDR <0.05). When analyzed with the aggregate scoring calculation, the miRNA that were most essential for regulating the DE mRNA included the following, all of which were downregulated post-ICH: miR-29a, miR-29b, miR-31, miR-34c, miR-125a, miR-132, miR-142, miR-150, miR-151a, miR-181a, and miR-186. A highly connected network of interactions was generated from these miRNA and their target mRNA. Conclusion: ICH strongly induced numerous miRNA/mRNA targets in swine PBMCs within six hours of onset. To our knowledge, this is the first integrated analysis of miRNA-seq and mRNA-seq in any study of ICH and the first report of miRNA in swine ICH. Further research is needed to determine whether these miRNA are potential therapeutic targets, including analyzing interventions such as miRNA overexpression or inhibition
2020-12-31 | GSE155242 | GEO
Project description:Transfer-RNA-Derived Small RNA (tsRNA) is s a novel class of short non-coding RNA including stress-induced tRNA fragments (tiRNA) and tRNA-derived fragments (tRF). Using RNA sequencing, we evaluated the tsRNA expression profiles in the brain of intracerebral hemorrhage (ICH) and sham rats at days 21. Meanwhile, tsRNA levels in ICH treated with the Traditional Chinese Medicine named Buyang Huanwu Decoction (BYHWD) were detected. Bioinformatics analyses indicated that tsRNAs were the important regulators in ICH and potential new therapeutic targets of BYHWD.
2018-04-26 | GSE109697 | GEO
Project description:Protein posttranslational modifications (PTMs) has been shown to regulate biological processes of human diseases via expanding the genetic code and for regulating cellular pathophysiology, however, the system-wide changes at the PTMs levels in ICH brain remains little known. Given that succinylation is one of the important PTMs in regulating many biological processes. Therefore, in this study, we used a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach to firstly investigated the ICH-associated brain protein succinyllysine modifications. We totally identified the concentration of approximately 6000 succinylation events and quantified approximately 3500 sites. Among them, 25 succinyllysine sites on 23 proteins were increased, while 13 succinyllysine sites on 12 proteins were downregulated after ICH. Additionally, the subcellular localization analysis of these significantly changed succinylproteins showed that 58.3% hyposuccinylated proteins were located in the mitochondria, while the percentage of succinylproteins located in mitochondria was decreased to about 35% in ICH brains with concomitant increasing in the percentage of cytoplasm to 30.4%. Further bioinformatic analysis showed that the succinylated proteins were mostly located in mitochondria and synapse-related subcellular spaces, and participate in many pathophysiological processes, such as metabolism, cytoskeleton organization, synapse working and ferroptosis, etc.. Moreover, we performed a combination analysis of our succinylproteomics data with previously published transcriptome data and found that most of the differentially succinylated proteins were distributed into neurons, endothelial cells and astrocytes. In conclusion, our analyses uncover a number of succinylation-affected processes and pathways in ICH brains and provide new insights for understanding ICH pathophysiological processes.
2021-10-29 | PXD025621 | Pride
Project description:The details of Toll-like receptor (TLR) 4 signaling affects protein succinylation in intracerebral hemorrhage (ICH) brains remains completely unclear. In this study, we constructed mice ICH models to investigate the changes in ICH-associated brain protein succinylation with the treatment of TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized a concentration of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase in 29 succinyllysine sites of 28 succinylated proteins and reduction of 24 succinyllysine sites on 23 succinylated proteins in ICH brains. Both the TAK242 treatment induced hypersuccinylated and hyposuccinylated proteins in ICH brains were mainly located in mitochondria and cytoplasm. GO analysis showed that TAK242 treatment induced changes in ICH-associated succinylated proteins were mostly located in synapse, membrane, vesicle, etc., and enriched in many processes, such as metabolism, synapse, myeline, etc.. KEGG analysis showed that TAK242 induced downregulation of succinylation was significantly linked to fatty acid metabolism and lysosome. Moreover, a combination analysis of our succinylproteomic data with previously published transcriptome data identified that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed into neurons, astrocytes and endothelial cells; and 7 and 3 of these succinylated proteins significantly high express in neurons and astrocytes, respectively. In conclusion, our analyses uncover a number of TLR4 signaling affected succinylation processes and pathways in mouse ICH brains and provide new insights for understanding ICH pathophysiological processes.
2021-11-03 | PXD025622 | Pride
Project description:Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.
2024-06-11 | GSE264394 | GEO