Institute of Clinical and Experimental Trauma Immunology, Ulm University Hospital, Helmholtzstr. 8/1, 89081 Ulm, Germany.
Department of Neurology, Ulm University Hospital, Oberer Eselsberg 45, 89081 Ulm, Germany.
Int J Mol Sci. 2022 Aug 25;23(17):9639. doi: 10.3390/ijms23179639.
Traumatic brain injury (TBI) represents a major determining factor of outcome in severely injured patients. However, reliable brain-damage-monitoring markers are still missing. We therefore assessed brain-specific beta-synuclein as a novel blood biomarker of synaptic damage and measured the benchmarks neurofilament light chain (NfL), as a neuroaxonal injury marker, and glial fibrillary acidic protein (GFAP), as an astroglial injury marker, in patients after polytrauma with and without TBI. Compared to healthy volunteers, plasma NfL, beta-synuclein, and GFAP were significantly increased after polytrauma. The markers demonstrated highly distinct time courses, with beta-synuclein and GFAP peaking early and NfL concentrations gradually elevating during the 10-day observation period. Correlation analyses revealed a distinct influence of the extent of extracranial hemorrhage and the severity of head injury on biomarker concentrations. A combined analysis of beta-synuclein and GFAP effectively discriminated between polytrauma patients with and without TBI, despite the comparable severity of injury. Furthermore, we found a good predictive performance for fatal outcome by employing the initial plasma concentrations of NfL, beta-synuclein, and GFAP. Our findings suggest a high diagnostic value of neuronal injury markers reflecting distinct aspects of neuronal injury for the diagnosis of TBI in the complex setting of polytrauma, especially in clinical surroundings with limited imaging opportunities.
创伤性脑损伤(TBI)是严重受伤患者结局的主要决定因素。然而,仍然缺乏可靠的脑损伤监测标志物。因此,我们评估了脑特异性β-突触核蛋白作为突触损伤的新型血液生物标志物,并测量了神经丝轻链(NfL)作为神经轴突损伤标志物和神经胶质纤维酸性蛋白(GFAP)作为星形胶质损伤标志物,在伴有和不伴有 TBI 的多发伤患者中。与健康志愿者相比,多发伤后患者的血浆 NfL、β-突触核蛋白和 GFAP 明显增加。这些标志物表现出高度不同的时间过程,β-突触核蛋白和 GFAP 早期达到峰值,NfL 浓度在 10 天观察期间逐渐升高。相关性分析显示,颅外出血程度和头部损伤严重程度对生物标志物浓度有明显影响。尽管损伤严重程度相当,但β-突触核蛋白和 GFAP 的联合分析可有效区分伴有和不伴有 TBI 的多发伤患者。此外,我们发现通过使用初始血浆 NfL、β-突触核蛋白和 GFAP 浓度可以很好地预测致命结局。我们的研究结果表明,反映神经元损伤不同方面的神经元损伤标志物具有很高的诊断价值,可用于诊断多发伤中 TBI,特别是在具有有限成像机会的临床环境中。