Chronic symptoms after mild traumatic brain injury (mTBI) are common among veterans and service members, and represent a significant source of morbidity, with those who sustain multiple mTBIs at greatest risk. Exosomal micro-RNAs (miRNAs), mediators of intercellular communication, may be involved in chronic TBI symptom persistence. Exosomal miRNA (exomiR) was extracted from 153 participants enrolled in the Chronic Effect of Neurotrauma Consortium (CENC) longitudinal study (no TBI, n = 35; ≥ 3 mTBIs (rTBI), n = 45; 1–2 mTBIs, n = 73). Analyses were performed with nCounter^® Human miRNA Expression Panels and Ingenuity Pathway Analysis (IPA) for identification of gene networks associated with TBI. Generalized linear models were used to analyze the predictive value of exomiR dysregulation and remote neurobehavioral symptoms. Compared with controls, there were 17 dysregulated exomiRs in the entire mTBI group and 32 dysregulated exomiRs in the rTBI group. Two miRNAs, hsa-miR-139-5p and hsa-miR-18a-5p, were significantly differentially expressed in the rTBI and 1–2 mTBI groups. IPA analyses showed that these dysregulated exomiRs correlated with pathways of inflammatory regulation, neurological disease, and cell development. Within the rTBI group, exomiRs correlated with gene activity for hub-genes of tumor protein TP53, insulin-like growth factor 1 receptor, and transforming growth factor beta. TBI history and neurobehavioral symptom survey scores negatively and significantly correlated with hsa-miR-103a-3p expression. Participants with remote mTBI have distinct exomiR profiles, which are significantly linked to inflammatory and neuronal repair pathways. These profiles suggest that analysis of exosomal miRNA expression may provide novel insights into the underlying pathobiology of chronic TBI symptom persistence.

中文翻译：

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轻度创伤性脑损伤军事人员中的外泌体 MicroRNA：神经创伤联盟生物标志物发现项目慢性影响的初步结果。


轻度创伤性脑损伤 (mTBI) 后的慢性症状在退伍军人和现役军人中很常见，是发病的重要来源，而那些遭受多次 mTBI 的人风险最大。外泌体微小 RNA (miRNA) 是细胞间通讯的介质，可能与慢性 TBI 症状持续存在有关。外泌体 miRNA (exomiR) 是从参加神经创伤联盟 (CENC) 纵向研究的 153 名参与者中提取的（无 TBI， n = 35；≥ 3 mTBI (rTBI)， n = 45；1–2 mTBI， n = 73） ）。使用 nCounter ^®人类 miRNA 表达面板和 Ingenuity Pathway Analysis (IPA) 进行分析，以鉴定与 TBI 相关的基因网络。使用广义线性模型来分析 exomiR 失调和远程神经行为症状的预测价值。与对照组相比，整个 mTBI 组中有 17 个失调的 exomiR，rTBI 组中有 32 个失调的 exomiR。两种 miRNA，hsa-miR-139-5p 和 hsa-miR-18a-5p，在 rTBI 和 1-2 mTBI 组中表达显着差异。 IPA 分析表明，这些失调的 exomiR 与炎症调节、神经系统疾病和细胞发育途径相关。在 rTBI 组中，exomiR 与肿瘤蛋白 TP53、胰岛素样生长因子 1 受体和转化生长因子 β 的中心基因的基因活性相关。 TBI病史和神经行为症状调查评分与hsa-miR-103a-3p表达呈负相关且显着相关。患有远程 mTBI 的参与者具有独特的 exomiR 特征，这与炎症和神经元修复途径显着相关。 这些概况表明，外泌体 miRNA 表达的分析可能为慢性 TBI 症状持续性的潜在病理学提供新的见解。