Traumatic brain injury (TBI) can have long-lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo-Dex were well tolerated in human and murine neural cells. Lipo-Dex showed significant suppression of inflammatory cytokines, IL-6 and TNF-α, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo-Dex were administered to young adult male and female C57BL/6 mice immediately after controlled cortical impact injury (a TBI model). Our findings demonstrate that Lipo-Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of pro-inflammatory cytokines, and microglial activation compared to Lipo-treated mice in a sex-dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano-therapies for brain injury. These results suggest that Lipo-Dex administration may effectively treat acute TBI.

中文翻译：

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脂质体递送地塞米松后小鼠创伤性脑损伤结果的性别依赖性改善

创伤性脑损伤（TBI）由于其强烈的炎症反应引起神经退行性变，可能会产生长期的身体、情感和认知后果。尽管康复治疗取得了进步，但 TBI 患者仍缺乏有效的神经保护治疗。此外，目前治疗 TBI 的药物输送方法在针对发炎的大脑区域方面效率低下。为了解决这个问题，我们开发了一种封装地塞米松 (Dex) 的脂质体纳米载体 (Lipo)，地塞米松 (Dex) 是糖皮质激素受体的激动剂，用于减轻各种情况下的炎症和肿胀。体外研究表明，Lipo-Dex 在人类和小鼠神经细胞中具有良好的耐受性。 Lipo-Dex 显示出显着抑制脂多糖诱导神经炎症后炎症细胞因子、IL-6 和 TNF-α 的释放。此外，在控制性皮质冲击损伤（TBI 模型）后立即对年轻成年雄性和雌性 C57BL/6 小鼠施用 Lipo-Dex。我们的研究结果表明，与 Lipo 治疗的小鼠相比，Lipo-Dex 可以选择性地靶向受损的大脑，从而以性别依赖性方式减少病变体积、细胞死亡、星形胶质细胞增生、促炎细胞因子的释放和小胶质细胞活化，显示出仅对雄性小鼠产生重大影响。这凸显了在开发和评估新的脑损伤纳米疗法时将性别视为关键变量的重要性。这些结果表明 Lipo-Dex 给药可以有效治疗急性 TBI。