Data from: Plasma metabolomic biomarkers accurately classify acute mild traumatic brain injury from controls

Past and recent attempts at devising objective biomarkers for traumatic brain injury (TBI) in both blood and cerebrospinal fluid have focused on abundance measures of time-dependent proteins. Similar independent determinants would be most welcome in diagnosing the most common form of TBI, mild TBI (mTBI), which remains difficult to define and confirm based solely on clinical criteria. There are currently no consensus diagnostic measures that objectively define individuals as having sustained an acute mTBI. Plasma metabolomic analyses have recently evolved to offer an alternative to proteomic analyses, offering an orthogonal diagnostic measure to what is currently available. The purpose of this study was to determine whether a developed set of metabolomic biomarkers is able to objectively classify college athletes sustaining mTBI from non-injured teammates, within 6 hours of trauma and whether such a biomarker panel could be effectively applied to an independent cohort of TBI and control subjects.
A 6-metabolite panel was developed from biomarkers that had their identities confirmed using tandem mass spectrometry (MS/MS) in our Athlete cohort. These biomarkers were defined at ≤6 hours following mTBI and objectively classified mTBI athletes from teammate controls, and provided similar classification of these groups at the 2, 3, and 7 days post-mTBI. The same 6-metabolite panel, when applied to a separate, independent cohort provided statistically similar results despite major differences between the two cohorts. Our confirmed plasma biomarker panel objectively classifies acute mTBI cases from controls within 6 hours of injury in our two independent cohorts. While encouraged by our initial results, we expect future studies to expand on these initial observations.

过往及近期针对创伤性脑损伤（traumatic brain injury, TBI）在血液与脑脊液中开发客观生物标志物的尝试，均聚焦于时间依赖性蛋白的丰度检测。目前针对最常见的TBI类型——轻度创伤性脑损伤（mild TBI, mTBI），仍亟需独立的客观诊断指标；此类损伤仅凭临床标准难以明确界定与确诊，目前尚无共识性的客观诊断方法可用于判定个体是否罹患急性mTBI。
近年来，血浆代谢组学分析技术逐步发展，可作为蛋白质组学分析的替代方案，为现有诊断手段提供一类正交的检测维度。本研究旨在验证：一套已开发的代谢组学生物标志物组套，能否在创伤发生后6小时内，准确区分罹患mTBI的大学生运动员与未受伤的队友；同时验证该生物标志物组套是否可有效应用于另一独立的TBI患者与对照受试者队列。
研究团队在运动员队列中，通过串联质谱法（tandem mass spectrometry, MS/MS）确认了6种代谢物的身份，并以此构建了代谢物组套。该组套可在mTBI发生后≤6小时内，准确区分mTBI运动员与队友对照；且在mTBI后2、3及7天，同样可实现对两组人群的有效分类。将该6代谢物组套应用于另一独立队列时，尽管两个队列间存在显著差异，但其分类结果仍具备统计学一致性。
本研究证实，这套血浆生物标志物组套可在两个独立队列中，于损伤后6小时内客观区分急性mTBI患者与对照受试者。尽管初始研究结果令人振奋，但我们期待后续研究能进一步拓展此类发现。