Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. Inflammation after ICH contributes to clinical outcomes, but the relevant molecular mechanisms remain poorly understood. In studies of peripheral leukocyte counts and mRNA-sequencing (mRNA-seq), our group previously reported that monocytes and Interleukin-8 (IL-8) were important contributors to post-ICH inflammation. microRNA (miRNA) are powerful regulators of gene expression and promising therapeutic targets. We now report findings from an integrated analysis of miRNA-seq and mRNA-seq in peripheral blood mononuclear cells (PBMCs) from a swine ICH model. In 10 pigs, one PBMC sample was collected immediately prior to ICH induction and a second 6 h later; miRNA-seq and mRNA-seq were completed for each sample. An aggregate score calculation determined which miRNA regulated the differentially expressed mRNA. Networks of molecular interactions were generated for the combined miRNA/target mRNA. A total of 227 miRNA were identified, and 46 were differentially expressed after ICH (FDR < 0.05). The anti-inflammatory miR-181a was decreased post-ICH, and it was the most highly connected miRNA in the miRNA/mRNA bioinformatic network analysis. miR-181a has interconnected pathophysiology with IL-8 and monocytes; in prior studies, we found that IL-8 and monocytes contributed to post-ICH inflammation and ICH clinical outcome, respectively. miR-181a was a significant mediator of post-ICH inflammation and is promising for further study, including as a potential therapeutic target. This investigation also demonstrated feasible methodology for miRNA-seq/mRNA-seq analysis in swine that is innovative, and with unique challenges, compared with transcriptomics research in more established species.

脑出血 (ICH) 是一种严重的神经系统疾病，没有经过验证的治疗方法。ICH 后的炎症有助于临床结果，但相关的分子机制仍然知之甚少。在外周白细胞计数和 mRNA 测序 (mRNA-seq) 的研究中，我们小组先前报道单核细胞和白细胞介素 8 (IL-8) 是 ICH 后炎症的重要因素。microRNA (miRNA) 是基因表达的强大调节剂和有希望的治疗靶点。我们现在报告对来自猪 ICH 模型的外周血单核细胞 (PBMC) 中 miRNA-seq 和 mRNA-seq 的综合分析结果。在 10 头猪中，在 ICH 诱导前即刻和 6 小时后收集了一个 PBMC 样本；每个样本都完成了 miRNA-seq 和 mRNA-seq。总分计算确定了哪个 miRNA 调节了差异表达的 mRNA。为组合的 miRNA/目标 mRNA 生成了分子相互作用网络。共鉴定出 227 种 miRNA，其中 46 种在 ICH 后差异表达（FDR < 0.05）。ICH 后抗炎 miR-181a 减少，它是 miRNA/mRNA 生物信息学网络分析中连接度最高的 miRNA。miR-181a 与 IL-8 和单核细胞具有相互关联的病理生理学；在之前的研究中，我们发现 IL-8 和单核细胞分别导致 ICH 后炎症和 ICH 临床结果。miR-181a 是 ICH 后炎症的重要介质，有希望进一步研究，包括作为潜在的治疗靶点。