Neutrophil degranulation is increased at seven days after human intracerebral hemorrhage, but not at 72 h, and correlates with decreased miR-3613 and miR-3690

Background: The molecular mechanisms of inflammatory pathophysiology after intracerebral hemorrhage (ICH) are not well established. 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. Methods: Twenty-seven ICH patients were enrolled via 24/7 screening and peripheral blood sampled at < 24 h (baseline), 72 h (+/-12 h), and 7 days (+/- 2 days) from last known normal. mRNA-seq and miRNA-seq were assessed for differential expression (DE) between the time point comparisons. Pathways identified via enrichment analysis (STRING, Reactome, Ingenuity Pathway Analysis) were tested via paired t-test and principal component analysis (PCA). Correlations between miRNA/mRNA pairs were computed. Results: For DE mRNA at 72 h vs. baseline, the main enriched pathways pertained to neuronal function and synaptic transmission; prominent neuron-related genes from these pathways are also implicated in platelet activation. For 7 days vs. baseline, neutrophil degranulation and ribosomal biogenesis were the most enriched pathways; PCA also suggested neutrophil degranulation was the pathway most significantly different at 7 days vs. baseline compared with 72 h vs. baseline (p = 0.02). miR-3613 and miR-3690 had decreased expression at 7 days and were the miRNA most correlated with DE genes from the neutrophil degranulation pathway. Conclusion: Neutrophil degranulation was the prominent enriched pathway at 7 days after ICH and correlated with decreased miR-3613 and miR-3690. Further research is warranted of neutrophils in post-ICH inflammatory pathophysiology and functional validation studies of miR-3613 and miR-3690 as potential regulators of neutrophil degranulation after ICH.