Defining Biological Phenotypes of Mild Traumatic Brain Injury Using Saliva MicroRNA Profiles.
Defining Biological Phenotypes of Mild Traumatic Brain Injury Using Saliva MicroRNA Profiles.
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用唾液MicroRNA图谱确定轻度创伤性脑损伤的生物学表型。
DOI：
10.1089/neu.2022.0018
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发表时间：
2022-07
影响因子：
4.2
通讯作者：
Master, Christina L.
中科院分区：
文献类型：
--
作者：
Hicks, Steven D.;Leddy, John;Lichak, Brooke P.;Onks, Cayce;Dretsch, Michael;Tennant, Priscilla;Haider, Mohammad Nadir;Olympia, Robert P.;Zuckerman, Scott L.;Loeffert, Jayson;Loeffert, Andrea C.;Monteith, Chuck;Master, Christina L.
脑震荡是一种异质性损伤，主要依赖于主观症状报告进行患者评估和治疗。开发一种客观的生物学测试可以帮助脑震荡患者的表型分类，从而促进个性化治疗。这项前瞻性多中心研究采用唾液微核糖核酸（miRNA）水平将251名脑震荡患者分为生物亚组。使用miRNA生物簇，我们的目标是评估医学/人口统计学特征，症状以及平衡和认知功能测量的差异。最好地定义每个簇的miRNA用于鉴定表征每个簇的生理途径。251名参与者（平均年龄：18 ± 7岁; 57%为男性）根据22种miRNA水平最佳地分为10个簇。各组在年龄（χ2 = 19.1，p = 0.024）、唾液收集时损伤后天数（χ2 = 22.6; p = 0.007）和既往脑震荡次数（χ2 = 17.6，p = 0.040）方面存在差异。这些集群在疲劳的症状报告上也有所不同（χ2 = 17.7; p = 0.039）、意识模糊（χ2 = 22.3; p = 0.008）、记忆困难（χ2 = 22.0; p = 0.009）和入睡困难（χ2 = 17.2; p = 0.046），但不包括客观平衡或认知表现（p > 0.05）。定义脑震荡簇的miRNA调节16种生理通路，包括肾上腺素能信号传导、雌激素信号传导、脂肪酸代谢、GABA能信号传导、突触囊泡循环和转化生长因子（TGF）-β信号传导。这些结果表明，唾液miRNA水平可以根据与神经病学和药理学靶点相关的潜在生物学扰动对脑震荡个体进行分层。如果在更大的队列中得到验证，miRNA评估可以帮助个体化，生物学驱动的脑震荡治疗。
Concussion is a heterogeneous injury that relies predominantly on subjective symptom reports for patient assessment and treatment. Developing an objective, biological test could aid phenotypic categorization of concussion patients, leading to advances in personalized treatment. This prospective multi-center study employed saliva micro-ribonucleic acid (miRNA) levels to stratify 251 individuals with concussion into biological subgroups. Using miRNA biological clusters, our objective was to assess for differences in medical/demographic characteristics, symptoms, and functional measures of balance and cognition. The miRNAs that best defined each cluster were used to identify physiological pathways that characterized each cluster. The 251 participants (mean age: 18 ± 7 years; 57% male) were optimally grouped into 10 clusters based on 22 miRNA levels. The clusters differed in age (χ2 = 19.1, p = 0.024), days post-injury at the time of saliva collection (χ2 = 22.6; p = 0.007), and number of prior concussions (χ2 = 17.6, p = 0.040). The clusters also differed in symptom reports for fatigue (χ2 = 17.7; p = 0.039), confusion (χ2 = 22.3; p = 0.008), difficulty remembering (χ2 = 22.0; p = 0.009), and trouble falling asleep (χ2 = 17.2; p = 0.046), but not objective balance or cognitive performance (p > 0.05). The miRNAs that defined concussion clusters regulate 16 physiological pathways, including adrenergic signaling, estrogen signaling, fatty acid metabolism, GABAergic signaling, synaptic vesicle cycling, and transforming growth factor (TGF)-β signaling. These results show that saliva miRNA levels may stratify individuals with concussion based on underlying biological perturbations that are relevant to both symptomology and pharmacological targets. If validated in a larger cohort, miRNA assessment could aid individualized, biology-driven concussion treatment.
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影响因子：
26.1
作者：
Lumba-Brown A;Yeates KO;Sarmiento K;Breiding MJ;Haegerich TM;Gioia GA;Turner M;Benzel EC;Suskauer SJ;Giza CC;Joseph M;Broomand C;Weissman B;Gordon W;Wright DW;Moser RS;McAvoy K;Ewing-Cobbs L;Duhaime AC;Putukian M;Holshouser B;Paulk D;Wade SL;Herring SA;Halstead M;Keenan HT;Choe M;Christian CW;Guskiewicz K;Raksin PB;Gregory A;Mucha A;Taylor HG;Callahan JM;DeWitt J;Collins MW;Kirkwood MW;Ragheb J;Ellenbogen RG;Spinks TJ;Ganiats TG;Sabelhaus LJ;Altenhofen K;Hoffman R;Getchius T;Gronseth G;Donnell Z;O'Connor RE;Timmons SD
通讯作者：
Timmons SD
影响因子：
18.4
作者：
Harmon, Kimberly G.;Clugston, James R.;Roberts, William O.
通讯作者：
Roberts, William O.
影响因子：
26.1
作者：
Johnson, Jeremiah J.;Loeffert, Andrea C.;Hicks, Steven D.
通讯作者：
Hicks, Steven D.
影响因子：
1.9
作者：
Ellis, Michael J.;Leddy, John J.;Willer, Barry
通讯作者：
Willer, Barry
影响因子：
2.7
作者：
Howell, David R.;Kriz, Peter;Meehan, William P., III
通讯作者：
Meehan, William P., III