Traumatic brain injury has been described as the signature affliction of recent military conflicts and repetitive TBIs, particularly associated with military and athletic activities, typically result in more severe clinical effects. The majority of TBIs are mild, but they can result in long term cognitive deficits for which there is no effective treatment. One of the most significant deficits observed in TBI patients is memory loss, which suggests that TBI can induce pathological changes within the hippocampus. tert-butylhydroquinone (tBHQ) and pioglitazone activate the Nrf2 and PPAR-γ transcription factors, respectively, and both have been shown to be neuroprotective in model systems. We examined the morphological changes within the hippocampus following repetitive mild TBI and simultaneous treatment with both factors. We utilized a closed head injury mouse model with five injuries over 5 weeks. Our results showed marked morphological changes among the dendrites and dendritic spines of the neurons of the dentate gyrus of the hippocampus. We observed decreases in overall dendritic length, as well as in the quantity and density of dendritic spines. Our treatment partially ameliorated these effects, suggesting that the Nrf2 and PPAR-γ transcription factors may be important targets for future drug development in the treatment of TBI in humans.

创伤性脑损伤被描述为近期军事冲突和重复性 TBI 的标志性痛苦，特别是与军事和体育活动相关，通常会导致更严重的临床影响。大多数 TBI 是轻微的，但它们会导致长期的认知缺陷，并且没有有效的治疗方法。在 TBI 患者中观察到的最显着缺陷之一是记忆丧失，这表明 TBI 可以诱导海马内的病理变化。叔丁基对苯二酚 (tBHQ) 和吡格列酮分别激活 Nrf2 和 PPAR-γ 转录因子，并且在模型系统中均显示出神经保护作用。我们检查了重复轻度 TBI 和同时使用这两种因素治疗后海马内的形态变化。我们使用了一个封闭的头部受伤小鼠模型，在 5 周内有 5 次受伤。我们的研究结果表明，海马齿状回神经元的树突和树突棘发生了显着的形态变化。我们观察到总树突长度的减少，以及树突棘的数量和密度。我们的治疗部分改善了这些影响，表明 Nrf2 和 PPAR-γ 转录因子可能是未来药物开发治疗人类 TBI 的重要靶标。