Buonora John E, Yarnell Angela M, Lazarus Rachel C, Mousseau Michael, Latour Lawrence L, Rizoli Sandro B, Baker Andrew J, Rhind Shawn G, Diaz-Arrastia Ramon, Mueller Gregory P
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , USA ; U.S. Army Graduate Program in Anesthesia Nursing, Academy of Health Sciences, Joint Base San Antonio , Fort Sam Houston, TX , USA.
Behavioral Biology Branch, Center for Military Psychiatry and Neuroscience Research, Walter Reed Army Institute of Research , Silver Spring, MD , USA.
Front Neurol. 2015 Mar 30;6:68. doi: 10.3389/fneur.2015.00068. eCollection 2015.
Important challenges for the diagnosis and monitoring of mild traumatic brain injury (mTBI) include the development of plasma biomarkers for assessing neurologic injury, monitoring pathogenesis, and predicting vulnerability for the development of untoward neurologic outcomes. While several biomarker proteins have shown promise in this regard, used individually, these candidates lack adequate sensitivity and/or specificity for making a definitive diagnosis or identifying those at risk of subsequent pathology. The objective for this study was to evaluate a panel of six recognized and novel biomarker candidates for the assessment of TBI in adult patients. The biomarkers studied were selected on the basis of their relative brain-specificities and potentials to reflect distinct features of TBI mechanisms including (1) neuronal damage assessed by neuron-specific enolase (NSE) and brain derived neurotrophic factor (BDNF); (2) oxidative stress assessed by peroxiredoxin 6 (PRDX6); (3) glial damage and gliosis assessed by glial fibrillary acidic protein and S100 calcium binding protein beta (S100b); (4) immune activation assessed by monocyte chemoattractant protein 1/chemokine (C-C motif) ligand 2 (MCP1/CCL2); and (5) disruption of the intercellular adhesion apparatus assessed by intercellular adhesion protein-5 (ICAM-5). The combined fold-changes in plasma levels of PRDX6, S100b, MCP1, NSE, and BDNF resulted in the formulation of a TBI assessment score that identified mTBI with a receiver operating characteristic (ROC) area under the curve of 0.97, when compared to healthy controls. This research demonstrates that a profile of biomarker responses can be used to formulate a diagnostic score that is sensitive for the detection of mTBI. Ideally, this multivariate assessment strategy will be refined with additional biomarkers that can effectively assess the spectrum of TBI and identify those at particular risk for developing neuropathologies as consequence of a mTBI event.
轻度创伤性脑损伤（mTBI）诊断和监测面临的重要挑战包括开发用于评估神经损伤、监测发病机制以及预测不良神经后果发生易感性的血浆生物标志物。虽然几种生物标志物蛋白在这方面已显示出前景，但单独使用时，这些候选物缺乏足够的敏感性和/或特异性来做出明确诊断或识别有后续病变风险的个体。本研究的目的是评估一组六种已认可和新型的生物标志物候选物，用于评估成年患者的创伤性脑损伤（TBI）。所研究的生物标志物是根据它们相对的脑特异性以及反映TBI机制不同特征的潜力来选择的，这些特征包括：（1）通过神经元特异性烯醇化酶（NSE）和脑源性神经营养因子（BDNF）评估的神经元损伤；（2）通过过氧化物酶体增殖物激活受体6（PRDX6）评估的氧化应激；（3）通过胶质纤维酸性蛋白和S100钙结合蛋白β（S100b）评估的胶质损伤和胶质增生；（4）通过单核细胞趋化蛋白1/趋化因子（C-C基序）配体2（MCP1/CCL2）评估的免疫激活；以及（5）通过细胞间粘附蛋白-5（ICAM-5）评估的细胞间粘附装置破坏。与健康对照相比，PRDX6、S100b、MCP1、NSE和BDNF血浆水平的联合倍数变化导致制定了一个TBI评估评分，该评分识别mTBI的受试者工作特征（ROC）曲线下面积为0.97。这项研究表明，生物标志物反应谱可用于制定对mTBI检测敏感的诊断评分。理想情况下，这种多变量评估策略将通过额外的生物标志物进行完善，这些生物标志物可以有效评估TBI的范围，并识别因mTBI事件而有发生神经病理学特定风险的个体。
