Caglayan Berrak, Kilic Ertugrul, Dalay Arman, Altunay Serdar, Tuzcu Mehmet, Erten Fusun, Orhan Cemal, Gunal Mehmet Yalcin, Yulug Burak, Juturu Vijaya, Sahin Kazim
Department of Medical Biology, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey.
Regenerative and Restorative Medical Research Center, Istanbul Medipol University, Istanbul, Turkey.
Mol Biol Rep. 2019 Feb;46(1):241-250. doi: 10.1007/s11033-018-4465-4. Epub 2018 Nov 8.
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently no FDA approved therapies. TBI results in oxidative stress due to the overproduction of reactive oxygen species and overwhelming of the endogenous antioxidant mechanisms. Recently, it has been reported that antioxidants including phytochemicals have a protective role against oxidative damage and inflammation after TBI. To analyze the effects of a naturally occurring antioxidant molecule, allyl isothiocyanate (AITC), on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways in TBI, a cryogenic injury model was induced in mice. Here, we showed that AITC administered immediately after the injury significantly decreased infarct volume and blood-brain barrier (BBB) permeability. Protein levels of proinflammatory cytokines interleukin-1β (IL1β) and interleukin-6 (IL6), glial fibrillary acidic protein (GFAP) and NF-κB were decreased, while Nrf2, growth-associated protein 43 (GAP43) and neural cell adhesion molecule levels were increased with AITC when compared with vehicle control. Our results demonstrated that the antioxidant molecule AITC, when applied immediately after TBI, provided beneficial effects on inflammatory processes while improving infarct volume and BBB permeability. Increased levels of plasticity markers, as well as an antioxidant gene regulator, Nrf2, by AITC, suggest that future studies are warranted to assess the protective activities of dietary or medicinal AITC in clinical studies.
创伤性脑损伤（TBI）是工业化国家年轻人和儿童死亡和发病的主要原因；然而，目前尚无美国食品药品监督管理局（FDA）批准的治疗方法。TBI由于活性氧的过度产生和内源性抗氧化机制的不堪重负而导致氧化应激。最近，有报道称包括植物化学物质在内的抗氧化剂对TBI后的氧化损伤和炎症具有保护作用。为了分析天然存在的抗氧化分子异硫氰酸烯丙酯（AITC）对TBI中核因子红细胞2相关因子2（Nrf2）和核因子κB（NF-κB）信号通路的影响，在小鼠中诱导了低温损伤模型。在此，我们表明损伤后立即给予AITC可显著降低梗死体积和血脑屏障（BBB）通透性。与载体对照相比，AITC可降低促炎细胞因子白细胞介素-1β（IL1β）和白细胞介素-6（IL6）、胶质纤维酸性蛋白（GFAP）和NF-κB的蛋白水平，同时增加Nrf2、生长相关蛋白43（GAP43）和神经细胞粘附分子水平。我们的结果表明，抗氧化分子AITC在TBI后立即应用时，对炎症过程具有有益作用，同时可改善梗死体积和BBB通透性。AITC使可塑性标志物以及抗氧化基因调节因子Nrf2的水平升高，这表明未来有必要在临床研究中评估饮食或药用AITC的保护活性。
