Safar Center for Resuscitation Research, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15224, United States; Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, United States.
Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15261, United States; Laboratory of Navigational Redox Lipidomics in Biomedicine, Department of Human Pathology, IM Sechenov First Moscow State Medical University, Russian Federation.
Free Radic Biol Med. 2018 Aug 20;124:493-503. doi: 10.1016/j.freeradbiomed.2018.06.031. Epub 2018 Jun 30.
Oxidative stress is a major contributor to secondary injury signaling cascades following traumatic brain injury (TBI). The role of lipid peroxidation in the pathophysiology of a traumatic insult to neural tissue is increasingly recognized. As the methods to quantify lipid peroxidation have gradually improved, so has the understanding of mechanistic details of lipid peroxidation and related signaling events in the injury pathogenesis. While free-radical mediated, non-enzymatic lipid peroxidation has long been studied, recent advances in redox lipidomics have demonstrated the significant contribution of enzymatic lipid peroxidation to TBI pathogenesis. Complex interactions between inflammation, phospholipid peroxidation, and hydrolysis define the engagement of different cell death programs and the severity of injury and outcome. This review focuses on enzymatic phospholipid peroxidation after TBI, including the mechanism of production, signaling roles in secondary injury pathology, and temporal course of production with respect to inflammatory response. In light of the newly identified phospholipid oxidation mechanisms, we also discuss possible therapeutic targets to improve neurocognitive outcome after TBI. Finally, we discuss current limitations in identifying oxidized phospholipids and possible methodologic improvements that can offer a deeper insight into the region-specific distribution and subcellular localization of phospholipid oxidation after TBI.
氧化应激是创伤性脑损伤（TBI）后继发性损伤信号级联反应的主要原因。脂质过氧化在神经组织创伤损伤发病机制中的作用越来越受到重视。随着定量脂质过氧化的方法逐渐改进，对脂质过氧化的机制细节以及相关信号事件在损伤发病机制中的作用的理解也逐渐深入。虽然自由基介导的非酶脂质过氧化作用早已被研究，但氧化脂质组学的最新进展表明，酶促脂质过氧化对 TBI 发病机制有重要贡献。炎症、磷脂过氧化和水解之间的复杂相互作用决定了不同细胞死亡程序的参与程度以及损伤和结果的严重程度。这篇综述重点介绍 TBI 后的酶促磷脂过氧化作用，包括其产生的机制、在继发性损伤病理学中的信号作用，以及与炎症反应相关的产生的时间过程。鉴于新发现的磷脂氧化机制，我们还讨论了可能的治疗靶点，以改善 TBI 后的神经认知预后。最后，我们讨论了目前在识别氧化磷脂方面的局限性，以及可能的方法改进，这些改进可以更深入地了解 TBI 后磷脂氧化的区域特异性分布和亚细胞定位。
