Biomarkers that can objectively guide the diagnosis of sports-related concussion, and consequent return-to-play decisions, are urgently needed. In this study, we aimed to determine the temporal profile and diagnostic ability of serum levels of neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP), and tau in concussed male and female Australian footballers. Blood was collected from 28 Australian rules footballers (20 males, 8 females) at 2-, 6-, and 13-days after a diagnosed concussion for comparison to their levels at baseline (i.e. pre-season), and with 27 control players (19 males, 8 females) without a diagnosis of concussion. Serum concentrations of protein markers associated with damage to neurons (UCHL1), axons (NfL, tau), and astrocytes (GFAP) were quantified using a Simoa HD-X Analyzer. Biomarker levels for concussed players were compared over time and between sex using generalised linear mixed effect models, and diagnostic performance was assessed using area under the receiver operating characteristic curve (AUROC) analysis. Serum NfL was increased from baseline in male footballers at 6- and 13-days post-concussion. GFAP and tau were increased in male footballers with concussion at 2- and 13-days respectively. NfL concentrations discriminated between concussed and non-concussed male footballers at all time-points (AUROC: 2d = 0.73, 6d = 0.85, 13d = 0.79), with tau also demonstrating utility at 13d (AUROC = 0.72). No biomarker differences were observed in female footballers after concussion. Serum NfL may be a useful biomarker for the acute and sub-acute diagnosis of concussion in males, and could inform neurobiological recovery and return-to-play decisions. Future adequately powered studies are still needed to investigate biomarker changes in concussed females.

中文翻译：

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男性澳大利亚足球运动员脑震荡后血清神经丝轻度升高

迫切需要能够客观地指导与运动有关的脑震荡的诊断以及随之而来的重返比赛决策的生物标记物。在这项研究中，我们旨在确定脑震荡的男性和女性澳大利亚人的神经丝轻蛋白（NfL），泛素羧基末端水解酶L1（UCHL1），神经胶质纤维酸性蛋白（GFAP）和tau的血清水平的时间变化和诊断能力足球运动员。在诊断为脑震荡后第2天，第6天和第13天从28名澳大利亚规则足球运动员（20名男性，8名女性）中采集血液，以与基线时（即赛季前）的水平进行比较，并与27名对照球员（男性19例，女性8例）未诊断为脑震荡。与神经元受损（UCHL1），轴突（NfL，tau）相关的蛋白质标记物的血清浓度 使用Simoa HD-X分析仪对星形胶质细胞（GFAP）进行定量。使用广义线性混合效应模型比较了随时间推移和性别之间脑震荡球员的生物标志物水平，并使用接受者工作特征曲线（AUROC）分析下的面积评估了诊断性能。脑震荡后6天和13天，男性足球运动员的血清NfL较基线水平升高。男性足球运动员在2天和13天脑震荡时GFAP和tau升高。NfL浓度在所有时间点上都区分了脑震荡和非脑震荡的男性足球运动员（AUROC：2d = 0.73，6d = 0.85，13d = 0.79），tau也表明效用在13d（AUROC = 0.72）。脑震荡后在女足球运动员中未观察到生物标志物差异。血清NfL可能是男性脑震荡的急性和亚急性诊断的有用生物标志物，并且可以为神经生物学恢复和恢复比赛决策提供信息。仍需要进行进一步研究，以研究脑震荡女性的生物标志物变化。