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: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: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:Spontaneous intracerebral hemorrhage (ICH) represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH) and the corresponding contralateral white (CW) and grey (CG) matter. Brain samples from 4 deceased patients who had a supratentorial intracerebral hemorrhage within the previous 4 days were included in the microarray study. This study group included 2 women and 2 men with a median age of 79 (68-92). On autopsy and during macroscopic exam, perihematomal areas suspected to present edema were identified by an experienced neuropathologist using last available neuroradiology images. Samples from perihematomal areas (PH), contralateral grey matter (CG) and contralateral white matter (CW) were obtained within the first 5 h after death and snap frozen in liquid nitrogen and stored at -80ºC until RNA isolation.
2010-09-23 | E-GEOD-24265 | biostudies-arrayexpress
Project description:Febuxostat is a urate-lowering medication for the treatment of patients with gout. This study was performed to elucidate the effects and underlying mechanisms of febuxostat on neuronal injury induced by intracerebral hemorrhage (ICH) in mice. The results showed that the administration of febuxostat improved neurological severity scores and blood-brain barrier (BBB) permeability. Moreover, febuxostat attenuated neuronal cell death and cytokine levels compared with the ICH group. Next, we conducted a transcriptome analysis of the neuroprotective effects of febuxostat. The overlapping significant differentially expressed genes (DEGs) were identified. Gene ontology (GO) analysis revealed that the overlapping significant DEGs were most enriched in five items. The intersecting DEGs of the aforementioned five pathways were Wisp1, Wnt7b, Frzb, and Pitx2. In addition, GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that DEGs were mainly involved in the wnt signaling pathway. Furthermore, the expression of Wisp1 and Wnt7b in the perihematomal region at 72 h post-ICH was observed. The results showed that both Wisp1 and Wnt7b were increased in the ICH group and were decreased by the administration of febuxostat. Taken together, the study showed that febuxostat protected against secondary brain injury after ICH and the Wnt7b-Wisp1 pathway was closely related to neuroprotective effects.
2022-06-09 | GSE193076 | GEO
Project description:We tested the hypothesis that circulating microRNAs (miRNAs) present in plasma might display a specific signature in patients with intracerebral hemorrhage (ICH). Global miRNA profiles were determined with the Agilent Human miRNA Microarray platform, 027233. ICH patients display a characteristic inflammation-related miRNA profile as compared to healthy controls. Plasma samples were collected from the following 6 subject groups: male ICH patients (n=8), female ICH patients (n=7), male healthy control (n=4), female healthy control (n=4), male ischemic stroke patients (n=8) and female ischemic stroke patients (n=8). Total RNAs isolated from 1 ml plasma were pooled for each group. A fixed volume of RNA sample was withdrawn from each pool and used for microarray detection.
2013-01-19 | E-GEOD-43618 | biostudies-arrayexpress