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Neutrophil Degranulation is Increased at Seven Days after Human Intracerebral Hemorrhage, but not at 72 Hours, and Correlates with Decreased miR-3613 and miR-3690

ABSTRACT: Intracerebral hemorrhage (ICH) occurs when there s spontaneous, non-traumatic bleeding into the brain and accounts for 50% of stroke-related mortality. We report mRNA-seq and miRNA-seq in the peripheral blood of ICH patients with three serial samples during the first week after the stroke. Twenty-seven ICH patients were enrolled via 24/7 screening and peripheral blood sampled at <24 hours (baseline), 72 hours (+/-12 hours), and 7 days (+/- 2days) from last known normal. mRNA-seq and miRNA-seq were assessed for differential expression (DE) between the time points and pathways identified via enrichment analysis as well as principal component analysis (PCA) were performed. Our analysis found that neutrophil degranulation was the prominent enriched pathway at 7 days after ICH. miR-3613 and miR-3690 are potential regulators of neutrophil degranulation after ICH.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296792 | GEO | 2025/08/18

REPOSITORIES: GEO

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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

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Neutrophil Degranulation is Increased at Seven Days after Human Intracerebral Hemorrhage, but not at 72 Hours, and Correlates with Decreased miR-3613 and miR-3690

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