Nkiliza Aurore, Huguenard Claire J C, Aldrich Gregory J, Ferguson Scott, Cseresznye Adam, Darcey Teresa, Evans James E, Dretsch Michael, Mullan Michael, Crawford Fiona, Abdullah Laila
Roskamp Institute, Sarasota, Florida, USA.
James A. Haley VA Hospital, Tampa, Florida, USA.
Neurotrauma Rep. 2023 Sep 25;4(1):643-654. doi: 10.1089/neur.2023.0045. eCollection 2023.
Currently approved blood biomarkers detect intracranial lesions in adult patients with mild to moderate traumatic brain injury (TBI) acutely post-injury. However, blood biomarkers are still needed to help with a differential diagnosis of mild TBI (mTBI) and post-traumatic stress disorder (PTSD) at chronic post-injury time points. Owing to the association between phospholipid (PL) dysfunction and chronic consequences of TBI, we hypothesized that examining bioactive PL metabolites (oxylipins and ethanolamides) would help identify long-term lipid changes associated with mTBI and PTSD. Lipid extracts of plasma from active-duty soldiers deployed to the Iraq/Afghanistan wars (control = 52, mTBI = 21, PTSD = 34, and TBI + PTSD = 13) were subjected to liquid chromatography/mass spectrometry analysis to examine oxylipins and ethanolamides. Linear regression analyses followed by comparisons were performed to assess the association of these lipids with diagnostic classifications. Significant differences were found in oxylipins derived from arachidonic acid (AA) between controls and mTBI, PTSD, and mTBI + PTSD groups. Levels of AA-derived oxylipins through the cytochrome P450 pathways and anandamide were significantly elevated among mTBI + PTSD patients who were carriers of the apolipoprotein E E4 allele. These studies demonstrate that AA-derived oxylipins and anandamide may be unique blood biomarkers of PTSD and mTBI + PTSD. Further, these AA metabolites may be indicative of an underlying inflammatory process that warrants further investigation. Future validation studies in larger cohorts are required to determine a potential application of this approach in providing a differential diagnosis of mTBI and PTSD in a clinical setting.
目前获批的血液生物标志物可在成年轻度至中度创伤性脑损伤（TBI）患者受伤后急性期检测出颅内病变。然而，仍需要血液生物标志物来帮助在受伤后的慢性时间点对轻度TBI（mTBI）和创伤后应激障碍（PTSD）进行鉴别诊断。由于磷脂（PL）功能障碍与TBI的慢性后果之间存在关联，我们推测检测生物活性PL代谢物（氧化脂质和乙醇酰胺）将有助于识别与mTBI和PTSD相关的长期脂质变化。对部署到伊拉克/阿富汗战争的现役士兵的血浆脂质提取物（对照组 = 52人，mTBI = 21人，PTSD = 34人，TBI + PTSD = 13人）进行液相色谱/质谱分析，以检测氧化脂质和乙醇酰胺。进行线性回归分析并随后进行比较，以评估这些脂质与诊断分类之间的关联。在对照组与mTBI、PTSD和mTBI + PTSD组之间，发现源自花生四烯酸（AA）的氧化脂质存在显著差异。在携带载脂蛋白E E4等位基因的mTBI + PTSD患者中，通过细胞色素P450途径产生的AA衍生氧化脂质和花生四烯酸乙醇胺水平显著升高。这些研究表明，AA衍生的氧化脂质和花生四烯酸乙醇胺可能是PTSD和mTBI + PTSD独特的血液生物标志物。此外，这些AA代谢物可能表明存在潜在的炎症过程，值得进一步研究。未来需要在更大的队列中进行验证研究，以确定这种方法在临床环境中对mTBI和PTSD进行鉴别诊断的潜在应用。
