Gene expression profiling and functional analysis in cerebral artery after experimental subarachnoid hemorrhage
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ABSTRACT:
ORGANISM(S): Oryctolagus cuniculus
SUBMITTER: Satoshi Matsuo
PROVIDER: E-GEOD-44910 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The molecular mechanisms of cerebral vasopasm after SAH are not totally understood. In the present study, we analyzed gene expression profile in rabbit basilar artery after SAH using cDNA microarrays.
2013-03-06 | GSE44910 | GEO
Project description:Purpose: Subarachnoid hemorrhage (SAH) is fatal in approximately 40% of cases. However, among survivors up to 95% experience permanent disabilities: post-SAH syndrome, which include impaired memory, executive functions, emotional and cognitive disturbances. Up to 45% of SAH patients are unable to continue with their professional activities. The long-term cognitive deficits result from morphological brain damage, including atrophy of the temporomesial/hippocampal area, which correlates with decreased neurocognitive scores. The mechanisms of the remote brain damage following SAH remain unknown, which hinders the progress in identifying new therapeutic targets. To unveil the leading mechanisms of permanent cognitive abnormalities following SAH and origin of atrophy of the temporomesial/hippocampal area, we analyzed SAH-induced specific hippocampal genomic pathways, which may lead to long term morphological damage. methods: Hippocampal RNA of SAH and Control groups, obtained 4 days after SAH induced by perforation of the circle of Willis in mice, was processed and sequenced. Using the next-generation RNA sequencing we determined differentially expressed genes in the bilateral whole hippocampus remote from SAH and applied different functional analyses and clustering tools to determine the main molecular pathways. Results: Differential gene expression analysis detected 642 upregulated and 398 down-regulated genes (false discovery rate <0.10) in SAH compared to Control group. Functional analyses using IPA suite, Gene Ontology terms, REACTOME pathways, and MsigDB Hallmark gene set collections revealed suppression of oligodendrocytes/myelin related genes, and overexpression of genes related to complement system along with genes related to innate and adaptive immunity, and extracellular matrix reorganization. Interferon regulatory factors, TGF-β1 and BMP, were identified as major orchestrating elements in the hippocampal tissue response. The MEME-Suite identified binding motifs of Krüppel-like factors, zinc finger transcription factors, and interferon regulatory factors as overrepresented DNA promoter motifs. Conclusion: Our findings suggest that damage of the entorhinal cortex by the subarachnoid blood remotely triggers specific hippocampal response, which may include suppression of oligodendrocytes functioning due to anterograde degeneration of hippocampal afferents accompanied. Identification of the prominent molecular hippocampal pathways may lead to the development of new therapeutic approaches for the treatment of long-term SAH consequences.
2021-08-11 | GSE167110 | GEO
Project description:Microglia-mediated neuroinflammatory response in the early brain injury after subarachnoid hemorrhage (SAH) has been reported to have an impact on progress and the mechanism is not completely understood. Here, we performed genome-wide transcriptome analysis of microglia purified from damaged hemisphere of adult mice at 3 days after SAH or sham operation. Robust transcriptional changes were observed between SAH-induced and healthy microglia, indicating rapid activation of microglia after suffering SAH. We identified 1576 differentially expressed genes (DEGs; 928 up-regulated and 648 down-regulated) in SAH-induced microglia compared with sham microglia, representing a strong alteration of the genome (6.85% of total ~23,000 genes). Functional enrichment of these DEGs indicated that cell division, inflammatory response, cytokine production and leukocyte chemotaxis were strongly activated in SAH-induced microglia. Moreover, we identified and proved the TLR2/IRF7 signaling axis was involved in regulation of this microglia-mediated inflammation in SAH mice, by performing flow cytometry, immunofluorescence. Together, these results provided a perspective of microglia-mediated neuroinflammatory response in the early stage of SAH and might give a new therapeutic target for SAH.
2021-06-30 | GSE167957 | GEO
Project description:We report the altered expression profiles of lncRNA and mRNA in mice cortex after subarachnoid hemorrhage (SAH). Total of 615 lncRNAs transcripts and 441 mRNAs transcripts were aberrantly expressed at 24 hours after SAH. SAH was induced in C57BL/6 mcie. The LncRNA and mRNA expression profiles in cortex of normal mice and SAH mice were examined by RNA-Seq.
2016-03-22 | E-GEOD-79416 | biostudies-arrayexpress
Project description:Microglial necroptosis exacerbates neurodegenerative diseases, central nervous system injury and demonstrates a pro-inflammatory process, but its contribution to subarachnoid hemorrhage (SAH) is poorly characterized. BCL-2 homologous antagonist-killer protein (Bak1), a critical regulatory molecule of endogenous apoptosis, can be involved in the pathological process of necroptosis by regulating mitochondrial permeability. In this study, we revealed microglia undergo necroptosis after subarachnoid hemorrhage in vivo and vitro. We found that Bak1 was elevated at 24h after SAH. Knocked-down of Bak1 by adeno-associated virus attenuates microglial necroptosis, alleviates neuroinflammation, and improves neurological function after SAH. To further explore the corresponding mechanisms, oxyhemoglobin induces necroptosis in BV2 microglia, increasing Bak1 expression and mediating pro-inflammatory phenotype transformation, exacerbating oxidative stress and neuroinflammation. Abrogating BV2 Bak1 reduces necroptosis by downregulating the expression of phosphorylated pseudokinase mixed lineage kinase domain-like protein (p-MLKL), then downregulates pro-inflammatory phenotype gene expression. RNA-Seq shows that disrupting BV2 Bak1 downregulates multiple immune and inflammatory pathways and ameliorates cell injury by elevating Thrombospondin 1 (THBS1) expression. In summary, we identified a critical regulatory role for Bak1 in microglial necroptosis and neuroinflammation after SAH. Bak1 is expected to be a new therapeutic target, and it provides a new idea for the treatment strategy of SAH.
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Project description:Delayed cerebral ischemia (DCI) is a dreadful complication present in up to 30% of patients with spontaneous subarachnoid hemorrhage (SAH). Indeed, DCI is one of the main causes of long-term disability in SAH, yet its prediction and prevention are troublesome in poor-grade SAH cases. In this prospective study, we explored the potential role of micro ribonucleic acid (microRNA, abbreviated miRNAs), – small non-coding RNAs involved in clue gene regulation at the post-transcriptional level – as biomarkers of neurological outcomes in SAH patients. We analyzed the expression of several miRNAs present in the cerebrospinal fluid (CSF) of SAH patients during the early stage of the disease (third-day post-hemorrhage). NanoString Technologies were used for the characterization of the CSF samples. We found an overexpression of miRNAs in the acute stage of 57 SAH in comparison with 10 non-SAH controls. Moreover, a differential expression of specific miRNAs was detected according to the severity of clinical onset, but also regarding the development of DCI and the midterm functional outcomes. These observations reinforce the potential utility of miRNAs as prognostic and diagnostic biomarkers in SAH patients. In addition, the identification of specific miRNAs related to SAH evolution might provide insights into their regulatory functions of pathophysiological pathways, such as the TGF-β inflammatory pathway and blood-brain barrier disruption
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Project description:Numerous studies have elucidated the neuroprotective effect of 6-gingerol in central nervous system diseases. However, the potential role and mechanism of 6-gingerol on early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains poorly understood. Here, we report that 6-gingerol exerts a neuroprotective effect on SAH-induced EBI through the GBP2/PI3K/AKT pathway. A SAH rat model was established by injecting femoral artery blood into the cisterna magna. 6-gingerol or vehicle was injected intraperitoneally one hour post-SAH induction. We found that the neurological function score and brain edema of SAH rats were significantly improved after 6-gingerol treatment, as well as neuronal apoptosis was attenuated in SAH rats by Nissl staining assay and TUNEL assay. To further explore potential molecular mechanisms associated with 6-gingerol, RNA sequencing was implemented to investigate the differences in transcriptomes between SAH rats with and without 6-gingerol treatment; and found that the expression of guanylate-binding protein 2 (GBP2) evidently was suppressed with 6-gingerol treatment compared to vehicle group. In addition, dual immunofluorescence was also employed to investigate changes in neurons, astrocytes, and microglia after 6-gingerol treatment. The results showed that GBP2 was expressed in neurons but not astrocytes or microglia. Western blotting analysis results demonstrated that the PI3K/AKT pathway was activated in the SAH rats treated with 6-gingerol. Furthermore, recombinant GBP2 protein and LY294002 (PI3K inhibitor) treatment reversed the effects of 6-gingerol treatment in SAH rats. These results indicate that 6-gingerol suppressed the expression of GBP2 to activate the PI3K/AKT pathway, improve neurologic outcomes, reduce brain edema and neuronal apoptosis. In summary, our findings suggest that 6-gingerol could attenuate EBI post-SAH in rats, and 6-gingerol may serve as a novel candidate neuroprotective drug for SAH-induced EBI.
2022-07-26 | GSE201312 | GEO
Project description:We report the altered expression profiles of lncRNA and mRNA in mice cortex after subarachnoid hemorrhage (SAH). Total of 617 lncRNAs transcripts and 444 mRNAs transcripts were aberrantly expressed at 24 hours after SAH.
2016-03-22 | GSE79416 | GEO
Project description:We used microarrays to profile the changes in gene signatures after 6 hours of subarachnoid haemorrhage in the rat cerebral arteries . Cerebral arteris of rats subjected to SAH or SHAM operated animals were isolated after 6 hours of SAH and total RNA was extracted for the array
2014-06-30 | E-GEOD-46696 | biostudies-arrayexpress
Project description:Brain injury resulting from hemorrhagic stroke is clinically challenging to manage and results in high rates of morbidity and mortality. The pathophysiology of brain damage resulting from aneurysmal subarachnoid hemorrhage (aSAH) is largely unknown, and methods to treat and monitor patients are variable with no meaningful correlations to patient outcome. Prediction of patient risk for serious neurological complications is currently a significant clinical obstacle. An extracellular RNA (exRNA) biomarker to predict onset and severity of brain damage would improve patient outcomes. We sequenced plasma and CSF samples from adult patients with SAH. Samples were collected from post bleed day 1 to day 7. Total exRNA was isolated from each sample. In addition, we prepared a subset of 140 CSF samples, isolating the RNA contained within extracellular vesicles and vesicle-depleted biofluid.
2018-10-27 | GSE121868 | GEO