The worldwide incidence of traumatic brain injury (TBI) is ∼0.5% per year and the frequency is significantly higher among military personnel and athletes. Repetitive TBIs are associated with military and athletic activities, and typically involve more severe consequences. The majority of TBIs are mild; however, these still can result in long-term cognitive deficits, and there is currently no effective treatment. tert-Butylhydroquinone (tBHQ) and pioglitazone can activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) transcription factors, respectively, and each has been shown to be neuroprotective in various model systems. We examined behavioral and gene expression changes after repetitive mild TBI followed by simultaneous treatment with both factors. We used a repetitive closed head injury of mice involving five injuries with a 1-week interval between each TBI. We found that memory performance was significantly reduced by the injuries, unless the TBIs were followed by the tBHQ and pioglitazone administrations. Certain genes; for example, growth hormone and osteopontin, were downregulated by the injury, and this was reversed by the treatment, whereas other genes; for example, a tumor necrosis factor receptor, were upregulated by the injury and restored if the post-injury treatment was administered. Analysis of gene expression levels affected by the injury and/or the treatment point to potential mechanisms that could be exploited therapeutically.

中文翻译：

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重复性轻度创伤性脑损伤和转录因子调节。

世界范围内创伤性脑损伤 (TBI) 的发病率约为每年 0.5%，并且军事人员和运动员的发病率明显更高。重复性脑外伤与军事和体育活动有关，通常会带来更严重的后果。大多数 TBI 是轻度的；然而，这些仍然会导致长期的认知缺陷，目前还没有有效的治疗方法。叔丁基对苯二酚 (tBHQ) 和吡格列酮可分别激活核因子（红细胞衍生 2）样 2 (Nrf2) 和过氧化物酶体增殖物激活受体-γ (PPAR-γ) 转录因子，并且每种都已被证明是各种模型系统中的神经保护作用。我们检查了重复轻度 TBI 后的行为和基因表达变化，然后同时使用这两种因素进行治疗。我们对小鼠进行了重复性闭合性头部损伤，涉及五次损伤，每次 TBI 之间间隔 1 周。我们发现记忆力因受伤而显着降低，除非 TBI 之后是 tBHQ 和吡格列酮给药。某些基因；例如，生长激素和骨桥蛋白因损伤而被下调，而这被治疗逆转，而其他基因；例如，肿瘤坏死因子受体会因损伤而上调，如果进行损伤后治疗，则会恢复。对受损伤和/或治疗影响的基因表达水平的分析指出了可用于治疗的潜在机制。我们发现记忆力因受伤而显着降低，除非 TBI 之后是 tBHQ 和吡格列酮给药。某些基因；例如，生长激素和骨桥蛋白因损伤而被下调，而这被治疗逆转，而其他基因；例如，肿瘤坏死因子受体会因损伤而上调，如果进行损伤后治疗，则会恢复。对受损伤和/或治疗影响的基因表达水平的分析指出了可用于治疗的潜在机制。我们发现记忆力因受伤而显着降低，除非 TBI 之后是 tBHQ 和吡格列酮给药。某些基因；例如，生长激素和骨桥蛋白因损伤而被下调，而这被治疗逆转，而其他基因；例如，肿瘤坏死因子受体会因损伤而上调，如果进行损伤后治疗，则会恢复。对受损伤和/或治疗影响的基因表达水平的分析指出了可用于治疗的潜在机制。一种肿瘤坏死因子受体，被损伤上调，如果进行损伤后治疗，则恢复。对受损伤和/或治疗影响的基因表达水平的分析指出了可用于治疗的潜在机制。一种肿瘤坏死因子受体，被损伤上调，如果进行损伤后治疗，则恢复。对受损伤和/或治疗影响的基因表达水平的分析指出了可用于治疗的潜在机制。