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较高的外泌体tau蛋白、β淀粉样蛋白42和白细胞介素-10与军事人员的轻度创伤性脑损伤及慢性症状相关。

Higher exosomal tau, amyloid-beta 42 and IL-10 are associated with mild TBIs and chronic symptoms in military personnel.

作者信息

Gill Jessica, Mustapic Maja, Diaz-Arrastia Ramon, Lange Rael, Gulyani Seema, Diehl Tom, Motamedi Vida, Osier Nicole, Stern Robert A, Kapogiannis Dimitrios

机构信息

a Tissue Injury Branch, National Institutes of Health, National Institute of Nursing Research , Bethesda , MD , United States.

b Aging, National Institutes of Health, National Institute of Aging , Baltimore , MD , United States.

出版信息

Brain Inj. 2018;32(10):1277-1284. doi: 10.1080/02699052.2018.1471738. Epub 2018 Jun 18.

Abstract

OBJECTIVE

Identify biomarkers in peripheral blood that relate to chronic post-concussive and behavioural symptoms following traumatic brain injuries (TBIs) to ultimately improve clinical management.

RESEARCH DESIGN

We compared military personnel with mild TBIs (mTBIs) (n = 42) to those without TBIs (n = 22) in concentrations of tau, amyloid-beta (Aβ42) and cytokines (tumour necrosis factor alpha (TNFα, interleukin (IL)-6 and -10) in neuronal-derived exosomes from the peripheral blood. We utilized nanosight technology coupled with ultra-sensitivity immunoassay methods. We also examined the impact of post-concussive and behavioural symptoms including depression and post-traumatic stress disorder (PTSD) on these neuronal-derived markers.

RESULTS

We report that concentrations of exosomal tau (F = 10.50), Aβ42 (F = 5.32) and IL-10 (F = 4.32) were elevated in the mTBI group compared to the controls. Within the mTBI group, regression models show that post-concussive symptoms were most related to exosomal tau elevations, whereas exosomal IL-10 levels were related to PTSD symptoms.

CONCLUSIONS

These findings suggest that chronic post-concussive symptoms following an mTBI relate to altered exosomal activity, and that greater tau pathology may underlie chronic post-concussive symptoms that develop following mTBIs. It also suggests that central inflammatory activity contributes to PTSD symptoms following an mTBI, providing necessary insights into the role of inflammation in chronic PTSD symptoms.

摘要

目的

识别外周血中与创伤性脑损伤(TBI)后的慢性脑震荡后症状及行为症状相关的生物标志物,以最终改善临床管理。

研究设计

我们比较了轻度创伤性脑损伤(mTBI)的军人(n = 42)和无创伤性脑损伤的军人(n = 22)外周血中神经元衍生外泌体中的tau、淀粉样β蛋白(Aβ42)和细胞因子(肿瘤坏死因子α(TNFα)、白细胞介素(IL)-6和-10)的浓度。我们采用了纳米可视技术与超灵敏免疫测定方法。我们还研究了脑震荡后症状及包括抑郁和创伤后应激障碍(PTSD)在内的行为症状对这些神经元衍生标志物的影响。

结果

我们报告,与对照组相比,mTBI组中外泌体tau(F = 10.50)、Aβ42(F = 5.32)和IL-10(F = 4.32)的浓度升高。在mTBI组中,回归模型显示,脑震荡后症状与外泌体tau升高最相关,而外泌体IL-10水平与PTSD症状相关。

结论

这些发现表明,mTBI后的慢性脑震荡后症状与外泌体活性改变有关,并且更大的tau病理学可能是mTBI后出现的慢性脑震荡后症状的基础。这也表明中枢炎症活动导致mTBI后的PTSD症状,为炎症在慢性PTSD症状中的作用提供了必要的见解。

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