Mondello Stefania, Guedes Vivian A, Lai Chen, Jeromin Andreas, Bazarian Jeffrey J, Gill Jessica M
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
National Institutes of Health, National Institute of Nursing Research, Bethesda, MD, United States.
Front Neurol. 2020 Jul 7;11:651. doi: 10.3389/fneur.2020.00651. eCollection 2020.
Sex differences in molecular biomarkers after sports-related concussion (SRC) could steadily advance our understanding of injury heterogeneity and complexity, and help capture phenotypic characteristics, by unveiling sex-dependent pathobiological processes and disease mechanisms. Such knowledge will help improve diagnosis, clinical management, and prognosis. Total-tau (t-tau) has recently emerged as a promising blood marker showing sex-associated differences in neurodegenerative diseases. Nonetheless, to date, little is known about the potential influence of sex on its injury-related concentration and dynamics after SRC. We hypothesized that measurements of circulating levels of t-tau over time would reflect a differential vulnerability signature, providing insights into the sex-related phenotypes and their relationship with clinical outcomes. To test this hypothesis, plasma levels of t-tau were measured using an ultrasensitive immunoassay up to 7 days after injury, in 46 concussed athletes (20 males, 26 females). We used trajectory analysis to generate two distinct temporal profiles of t-tau, which were then compared with gender and return to play (RTP). The majority of subjects (~63%) started with low t-tau concentrations that further declined within the first 48 h; while the remaining ("maximal decliners") started with concentrations comparable to the baseline levels that also fell over time, but persisting markedly higher compared with the first profile. The maximal decliner group was primarily composed of female subjects ( = 0.007) and was significantly associated with poor outcome (RTP ≥ 10 days after concussion) ( = 0.011). Taken together, our data provide evidence for the existence of sex-related biosignatures following sports-related concussions, possibly indicating a differential effect as a result of distinct brain vulnerability and inherent injury response. Future studies will be required to further elucidate underlying sex-based biological and pathophysiological mechanisms, and determine the value of t-tau signatures for management and therapeutic decision-making in sports-related concussions.
运动性脑震荡（SRC）后分子生物标志物的性别差异可以通过揭示性别依赖性病理生物学过程和疾病机制，稳步推进我们对损伤异质性和复杂性的理解，并有助于捕捉表型特征。这些知识将有助于改善诊断、临床管理和预后。总tau蛋白（t-tau）最近已成为一种有前景的血液标志物，在神经退行性疾病中显示出与性别相关的差异。然而，迄今为止，关于性别对SRC后其损伤相关浓度和动态的潜在影响知之甚少。我们假设，随着时间的推移测量循环中t-tau的水平将反映出不同的易损性特征，从而深入了解与性别相关的表型及其与临床结果的关系。为了验证这一假设，我们使用超灵敏免疫测定法在损伤后7天内测量了46名脑震荡运动员（20名男性，26名女性）血浆中t-tau的水平。我们使用轨迹分析生成了两种不同的t-tau时间曲线，然后将其与性别和恢复比赛（RTP）情况进行比较。大多数受试者（约63%）开始时t-tau浓度较低，在最初48小时内进一步下降；而其余受试者（“最大下降者”）开始时的浓度与基线水平相当，随着时间的推移也会下降，但与第一种情况相比仍显著较高。最大下降者组主要由女性受试者组成（P = 0.007），并且与不良结果（脑震荡后RTP≥10天）显著相关（P = 0.011）。综上所述，我们的数据为运动性脑震荡后存在与性别相关的生物标志物提供了证据，这可能表明由于不同的脑易损性和固有的损伤反应而产生的差异效应。未来需要进一步研究以阐明潜在的基于性别的生物学和病理生理机制，并确定t-tau标志物在运动性脑震荡管理和治疗决策中的价值。
