Background:Traumatic brain injury (TBI) has been a serious public health issue. Clinically, there is an urgent need for agents to ameliorate the neuroinflammation and oxidative stress induced by TBI. Our previous research has demonstrated that quercetin could protect the neurological function. However, the detailed mechanism underlying this process remains poorly understood. Objective:This research was designed to investigate the mechanisms of quercetin to protect the cortical neurons. Methods:A modified weight-drop device was used for the TBI model. 5, 20 or 50 mg/kg quercetin was injected intraperitoneally to rats at 0.5, 12 and 24 h post TBI. Rats were sacrificed three days post injury and their cerebral cortex was obtained from the injured side. The rats were randomly assigned into three groups of equal number: TBI and quercetin group, TBI group, and Sham group. The brain water content was calculated to estimate the brain damage induced by TBI. Immunohistochemical and Western blot assays were utilized to investigate the neurobehavioral status. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction were performed to evaluate the inflammatory responses. The cortical oxidative stress was measured by estimating the activities of malondialdehyde, superoxide dismutase, catalase and glutathione-Px. Western blot was utilized to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). Results:Quercetin attenuated the brain edema and microgliosis in TBI rats. Quercetin treatment attenuated cortical inflammatory responses and oxidative stress induced by TBI insults. Quercetin treatment activated the cortical Nrf2/HO-1 pathway in TBI rats. Conclusions:Quercetin ameliorated the TBI-induced neuroinflammation and oxidative stress in the cortex through activating the Nrf2/HO-1 pathway.

中文翻译：

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槲皮素通过激活Nrf2/HO-1通路对创伤性脑损伤诱导的皮层炎症和氧化应激的保护作用

背景：创伤性脑损伤 (TBI) 已成为严重的公共卫生问题。临床上，迫切需要改善由 TBI 诱导的神经炎症和氧化应激的药物。我们之前的研究表明，槲皮素可以保护神经功能。然而，这一过程背后的详细机制仍然知之甚少。目的：本研究旨在探讨槲皮素保护皮质神经元的机制。方法：采用改良的减重装置制作TBI模型。在 TBI 后 0.5、12 和 24 小时向大鼠腹膜内注射 5、20 或 50 mg/kg 槲皮素。损伤后三天处死大鼠，并从受伤侧获得它们的大脑皮层。将大鼠随机分为三组，数量相等：TBI组和槲皮素组，TBI 组和 Sham 组。计算脑水含量以估计由 TBI 引起的脑损伤。免疫组织化学和蛋白质印迹分析被用来研究神经行为状态。进行酶联免疫吸附测定和逆转录聚合酶链反应以评估炎症反应。通过估计丙二醛、超氧化物歧化酶、过氧化氢酶和谷胱甘肽-Px 的活性来测量皮质氧化应激。蛋白质印迹用于评估核因子红细胞 2 相关因子 2 (Nrf-2) 和血红素加氧酶 1 (HO-1) 的表达。结果：槲皮素可减轻TBI大鼠脑水肿和小胶质细胞增生。槲皮素治疗减弱了由 TBI 损伤诱导的皮质炎症反应和氧化应激。槲皮素治疗激活了 TBI 大鼠的皮质 Nrf2/HO-1 通路。结论：槲皮素通过激活 Nrf2/HO-1 通路改善 TBI 诱导的皮层神经炎症和氧化应激。