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脑震荡后与恢复运动相关的血浆生物标志物的蛋白质组学分析:美国大学体育协会和国防部CARE联盟的研究结果

Proteomic Profiling of Plasma Biomarkers Associated With Return to Sport Following Concussion: Findings From the NCAA and Department of Defense CARE Consortium.

作者信息

Vorn Rany, Mithani Sara, Devoto Christina, Meier Timothy B, Lai Chen, Yun Sijung, Broglio Steven P, McAllister Thomas W, Giza Christopher C, Kim Hyung-Suk, Huber Daniel, Harezlak Jaroslaw, Cameron Kenneth L, McGinty Gerald, Jackson Jonathan, Guskiewicz Kevin M, Mihalik Jason P, Brooks Alison, Duma Stefan, Rowson Steven, Nelson Lindsay D, Pasquina Paul, McCrea Michael A, Gill Jessica M

机构信息

School of Nursing, Johns Hopkins University, Baltimore, MD, United States.

National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United States.

出版信息

Front Neurol. 2022 Jul 19;13:901238. doi: 10.3389/fneur.2022.901238. eCollection 2022.

Abstract

OBJECTIVE

To investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).

METHODS

This multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes ( = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery <14-days ( = 99) and (2) recovery ≥14-days ( = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with <14-days and ≥14-days.

RESULTS

We identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery <14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling.

CONCLUSION

Our data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a <14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions.

摘要

目的

研究血浆蛋白质组学图谱,以识别与运动相关脑震荡(SRC)后恢复运动(RTS)相关的生物标志物。

方法

本多中心、前瞻性、病例对照研究是美国国家大学体育协会-国防部脑震荡评估、研究和教育(CARE)联盟进行的一项更大队列研究的一部分,纳入了受伤后48小时内采血且报告已恢复至无症状的运动员(n = 140),分为两组:(1)恢复时间<14天(n = 99)和(2)恢复时间≥14天(n = 41)。我们应用了一种高度多重的蛋白质组学技术,该技术使用DNA适体分析法靶向受伤后<14天和≥14天的脑震荡运动员血浆样本中的1305种蛋白质。

结果

我们发现,与恢复时间<14天的组相比,恢复时间≥14天的脑震荡运动员中有87种血浆蛋白显著失调(32种上调,55种下调)。将这些显著失调的蛋白质上传至 Ingenuity Pathway Analysis(IPA)软件进行分析。通路分析表明,显著失调的蛋白质与STAT3通路、生长因子对上皮-间质转化的调节通路以及急性期反应信号传导有关。

结论

我们的数据表明,对受伤后<14天和≥14天恢复的脑震荡运动员进行大规模血浆蛋白质组学分析是可行的。这些发现为神经生物学恢复的病理生理机制提供了一种可能的理解。需要进一步研究以确定这些蛋白质是否能帮助临床医生做出恢复运动的决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306c/9343581/9c969dec8762/fneur-13-901238-g0001.jpg

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