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Inflammatory Cytokines Associate With Neuroimaging After Acute Mild Traumatic Brain Injury.
Frontiers in Neurology ( IF 3.4 ) Pub Date : 2020-05-19 , DOI: 10.3389/fneur.2020.00348
Katie A Edwards 1, 2 , Cassandra L Pattinson 1 , Vivian A Guedes 1 , Jordan Peyer 1 , Candace Moore 1 , Tara Davis 3, 4 , Christina Devoto 1, 2 , L Christine Turtzo 5 , Lawrence Latour 5 , Jessica M Gill 1, 6
Affiliation  

Introduction: Elevated levels of blood-based proinflammatory cytokines are linked to acute moderate to severe traumatic brain injuries (TBIs), yet less is known in acute mild (m)TBI cohorts. The current study examined whether blood-based cytokines can differentiate patients with mTBI, with and without neuroimaging findings (CT and MRI). Material and Methods: Within 24 h of a mTBI, determined by a Glasgow Coma Scale (GCS) between 13 and 15, participants (n = 250) underwent a computed tomography (CT) and magnetic resonance imaging (MRI) scan and provided a blood sample. Participants were classified into three groups according to imaging findings; (1) CT+, (2) MRI+ (CT-), (3) Controls (CT- MRI-). Plasma levels of circulating cytokines (IL-6, IL-10, TNFα), and vascular endothelial growth factor (VEGF) were measured using an ultra-sensitive immunoassay. Results: Concentrations of inflammatory cytokines (IL-6, TNFα) and VEGF were elevated in CT+, as well as MRI+ groups (p < 0.001), compared to controls, even after controlling for age, sex and cardiovascular disease (CVD)-related risk factors; hypertension, and hyperlipidemia. Post-concussive symptoms were associated with imaging groupings, but not inflammatory cytokines in this cohort. Levels of VEGF, IL-6, and TNFα differentiated patients with CT+ findings from controls, with the combined biomarker model (VEGF, IL-6, TNFα, and IL-10) showing good discriminatory power (AUC 0.92, 95% CI 0.87-0.97). IL-6 was a fair predictor of MRI+ findings compared to controls (AUC 0.70, 95% CI 0.60-0.78). Finally, the combined biomarker model discriminated patients with MRI+ from CT+ with an AUC of 0.71 (95% CI 0.62-0.80). Conclusions: When combined, IL-6, TNFα, and VEGF may provide a promising biomarker cytokine panel to differentiate mTBI patients with CT+ imaging vs. controls. Singularly, IL-6 was a fair discriminator between each of the imaging groups. Future research directions may help elucidate mechanisms related to injury severity and potentially, recovery following an mTBI.

中文翻译:

急性轻度颅脑外伤后炎症细胞因子与神经影像相关。

简介:血液中促炎性细胞因子水平升高与急性中度至重度颅脑损伤(TBI)有关,但在轻度(m)TBI急性队列中所知甚少。目前的研究检查了基于血液的细胞因子是否可以区分有或没有神经影像学检查(CT和MRI)的mTBI患者。材料和方法:在mTBI的24小时内,由格拉斯哥昏迷量表(GCS)在13至15之间确定,参与者(n = 250)进行了计算机断层扫描(CT)和磁共振成像(MRI)扫描,并提供了血液样品。根据影像学表现将参加者分为三类。(1)CT +,(2)MRI +(CT-),(3)对照(CT- MRI-)。使用超灵敏免疫测定法测量血浆循环细胞因子(IL-6,IL-10,TNFα)和血管内皮生长因子(VEGF)的水平。结果:与对照组相比,即使在控制了与年龄,性别和心血管疾病(CVD)相关的疾病后,与对照组相比,CT +组和MRI +组中炎症细胞因子(IL-6,TNFα)和VEGF的浓度也升高了(p <0.001)风险因素; 高血压和高脂血症。脑震荡后的症状与影像学分组有关,但在该队列中与炎性细胞因子无关。VEGF,IL-6和TNFα的水平与对照组相比具有CT +表现的患者有所区分,并且组合的生物标志物模型(VEGF,IL-6,TNFα和IL-10)显示出良好的辨别力(AUC 0.92,95%CI 0.87- 0.97)。与对照组相比,IL-6是MRI +发现的合理预测指标(AUC 0.70,95%CI 0.60-0.78)。最后,组合的生物标志物模型将CT +的MRI +患者与AUC为0.71(95%CI 0.62-0.80)的患者区分开。结论:IL-6联合使用时,TNFα和VEGF可能提供有前途的生物标志物细胞因子组,以区分具有CT +成像和对照的mTBI患者。单独地,IL-6是每个成像组之间的公平区分者。未来的研究方向可能有助于阐明与损伤严重程度以及潜在的mTBI恢复有关的机制。
更新日期:2020-05-19
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