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急性人类创伤性脑损伤中的血浆脂质特征:与神经元损伤和炎症标志物的联系。

A plasma lipid signature in acute human traumatic brain injury: Link with neuronal injury and inflammation markers.

作者信息

Nessel Isabell, Whiley Luke, Dyall Simon C, Michael-Titus Adina T

机构信息

Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Health Futures Institute, Murdoch University, Murdoch, Australia.

出版信息

J Cereb Blood Flow Metab. 2025 Mar;45(3):443-458. doi: 10.1177/0271678X241276951. Epub 2024 Aug 26.

Abstract

Traumatic brain injury (TBI) leads to major membrane lipid breakdown. We investigated plasma lipids over 3 days post-TBI, to identify a signature of acute human TBI and assess its correlation with neuronal injury and inflammation. Plasma from patients with TBI (Abbreviated Injury Scale (AIS)3 - serious injury, n = 5; AIS4 - severe injury, n = 8), and controls (n = 13) was analysed for lipidomic profile, neurofilament light (NFL) and cytokines, and the omega-3 index was measured in red blood cells. A lipid signature separated TBI from controls, at 24 and 72 h. Major species driving the separation were: lysophosphatidylcholine (LPC), phosphatidylcholine (PC) and hexosylceramide (HexCer). Docosahexaenoic acid (DHA, 22:6) and LPC (0:0/22:6) decreased post-injury. NFL levels were increased at 24 and 72 h post-injury in AIS4 TBI vs. controls. Interleukin (IL-)6, IL-2 and IL-13 were elevated at 24 h in AIS4 patients vs. controls. NFL and IL-6 were negatively correlated with several lipids. The omega-3 index at admission was low in all patients (controls: 4.3 ± 1.1% and TBI: 4.0 ± 1.1%) and did not change significantly over 3 days post-injury. We have identified specific lipid changes, correlated with markers of injury and inflammation in acute TBI. These observations could inform future lipid-based therapeutic approaches.

摘要

创伤性脑损伤(TBI)会导致主要膜脂分解。我们在TBI后的3天内对血浆脂质进行了研究,以确定急性人类TBI的特征,并评估其与神经元损伤和炎症的相关性。分析了TBI患者(简明损伤定级标准(AIS)3级——重伤,n = 5;AIS 4级——严重损伤,n = 8)和对照组(n = 13)的血浆脂质组学特征、神经丝轻链(NFL)和细胞因子,并测定了红细胞中的ω-3指数。在24小时和72小时时,一种脂质特征将TBI患者与对照组区分开来。导致这种区分的主要脂质种类有:溶血磷脂酰胆碱(LPC)、磷脂酰胆碱(PC)和己糖神经酰胺(HexCer)。损伤后二十二碳六烯酸(DHA,22:6)和LPC(0:0/22:6)减少。与对照组相比,AIS 4级TBI患者在损伤后24小时和72小时时NFL水平升高。与对照组相比,AIS 4级患者在24小时时白细胞介素(IL-)6、IL-2和IL-13升高。NFL和IL-6与几种脂质呈负相关。所有患者入院时的ω-3指数都较低(对照组:4.3±1.1%,TBI组:4.0±1.1%),且在损伤后3天内无显著变化。我们已经确定了急性TBI中与损伤和炎症标志物相关的特定脂质变化。这些观察结果可为未来基于脂质的治疗方法提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e18/11572080/205019fc50d0/10.1177_0271678X241276951-fig1.jpg

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