Salivary MicroRNAs: Diagnostic Markers of Mild Traumatic Brain Injury in Contact-Sport.
Salivary MicroRNAs: Diagnostic Markers of Mild Traumatic Brain Injury in Contact-Sport.
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DOI：
10.3389/fnmol.2018.00290
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发表时间：
2018
影响因子：
4.8
通讯作者：
Belli A
中科院分区：
文献类型：
--
作者：
Di Pietro V;Porto E;Ragusa M;Barbagallo C;Davies D;Forcione M;Logan A;Di Pietro C;Purrello M;Grey M;Hammond D;Sawlani V;Barbey AK;Belli A
脑震荡很难诊断，特别是当症状不典型或出现较晚时。准确和及时的初步评估对于临床管理至关重要。脑脊髓液（CSF）和血液标志物的创伤性脑损伤显示出有希望的结果，但其在脑震荡的临床应用有显着的局限性。在这项研究中，我们探索了唾液作为脑震荡生物标志物的新来源。在脑震荡后48-72小时收集脑震荡球员的唾液样本，并通过高通量技术进行分析。10名脑震荡橄榄球专业和半专业运动员和10名非脑震荡匹配对照的发现组用于通过Proseek多重炎症技术分析92种炎症蛋白。此外，6名脑震荡和6名非脑震荡运动员的唾液样本被用于通过Nanostring技术筛选800个人类microRNA（miRNAs）。然后通过RT-qPCR在包括22名脑震荡运动员的扩大队列（验证组）中验证结果。结果显示，在唾液中检测到的65种炎性蛋白在组间没有显著变化，但有5种microRNA，miR-27 b-3 p（p = 0.016），let-7i-5p（p = 0.001）、miR-142- 3 p（p = 0.008）、miR-107（p = 0.028）、miR-135 b-5 p（p = 0.017）在脑震荡运动员中显著上调。单变量ROC曲线分析显示，差异表达的miRNAs可作为脑震荡的良好分类指标。进一步的分析显示，这些microRNA与ImPACT脑震荡评估工具的反应时间组件之间存在显著相关性。此外，生物计算分析预测这些microRNA参与可能与创伤相关的重要生物过程，如对缺氧的反应，细胞死亡，神经发生，轴突修复和髓鞘形成。唾液样本的易获取性和非侵入性使得这些生物标志物特别适合于脑震荡评估。
Concussion is difficult to diagnose, particularly when symptoms are atypical or late in presenting. An accurate and timely initial assessment is crucial for clinical management. Cerebral spinal fluid (CSF) and blood markers of traumatic brain injury show promising results but their clinical applicability in concussion has significant limitations. In the study, we explored saliva as a new source of biomarkers of concussion. Saliva samples of concussed players were collected after 48–72 h from concussion and analyzed by high-throughput technologies. A discovery group of 10 concussed rugby professional and semiprofessional athletes and 10 non-concussed matched controls was used for the analysis of 92 inflammatory proteins by the Proseek-Multiplex-Inflammation technology. In addition, saliva samples of 6 concussed and 6 non-concussed athletes were used to screen 800 human microRNAs (miRNAs) by the Nanostring Technology. The results were then validated by RT-qPCR in an enlarged cohort (validation group) comprising 22 concussed athletes. Results showed, no significant variations of the 65 inflammatory proteins detected in saliva between groups but 5 microRNAs, miR-27b-3p (p = 0.016), let-7i-5p (p = 0.001), miR-142-3p (p = 0.008), miR-107 (p = 0.028), miR-135b-5p (p = 0.017) significantly upregulated in concussed athletes. Univariate ROC curve analysis showed that the differentially expressed miRNAs could be considered good classifiers of concussion. Further analyses showed significant correlation between these microRNAs and Reaction Time component of the ImPACT concussion assessment tool. In addition, biocomputation analysis predicted the involvement of these microRNAs in important biological processes that might be related to trauma, such as response to hypoxia, cell death, neurogenesis, axon repair and myelination. Ease of access and non-invasiveness of saliva samples make these biomarkers particularly suitable for concussion assessment.
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影响因子：
4.6
作者：
Bhomia M;Balakathiresan NS;Wang KK;Papa L;Maheshwari RK
通讯作者：
Maheshwari RK
影响因子：
4.3
作者：
Di Pietro, Valentina;Amorini, Angela M.;Belli, Antonio
通讯作者：
Belli, Antonio
影响因子：
4.2
作者：
Brophy, Gretchen M.;Mondello, Stefania;Wang, Kevin K. W.
通讯作者：
Wang, Kevin K. W.
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：
4.2
作者：
Di Pietro, Valentina;Ragusa, Marco;Belli, Antonio
通讯作者：
Belli, Antonio