Traumatic brain injury (TBI) is a leading cause of high mortality and disability worldwide. Overactivation of astrocytes and overexpression of inflammatory responses in the injured brain are characteristic pathological features of TBI. Rosiglitazone (ROS) is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist known for its anti-inflammatory activity. However, the relationship between the inflammatory response involved in ROS treatment and astrocyte A1 polarization remains unclear. This study aimed to investigate whether ROS treatment improves dysfunction and astrocyte polarization induced after TBI and to elucidate the underlying mechanisms of these functions. SD rats were randomly divided into sham operation group, TBI group, TBI+ROS group, and TBI+ PPAR-γ antagonist group (GW9662 + TBI). The rat TBI injury model was prepared by the CCI method; brain water content test and wire grip test scores suggested the prognosis; FJB staining showed the changes of ROS on the morphology and number of neurons in the peripheral area of cortical injury; ELISA, immunofluorescence staining, and western blotting analysis revealed the effects of ROS on inflammatory response and astrocyte activation with the degree of A1 polarization after TBI. Brain water content, inflammatory factor expression, and astrocyte activation in the TBI group were higher than those in the sham-operated group (P < 0.05); compared with the TBI group, the expression of the above indexes in the ROS group was significantly lower (P < 0.05). Compared with the TBI group, PPAR-γ content was significantly higher and C3 content was considerably lower in the ROS group (P < 0.05); compared with the TBI group, PPAR-γ content was significantly lower and C3 content was substantially higher in the inhibitor group (P < 0.05). ROS can exert neuroprotective effects by inhibiting astrocyte A1 polarization through the PPAR-γ pathway based on the reduction of inflammatory factors and astrocyte activation in the brain after TBI.

中文翻译：

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罗格列酮在实验性脑外伤后以 PPAR-γ 依赖性方式调节星形胶质细胞极化和神经炎症

创伤性脑损伤（TBI）是全世界高死亡率和高残疾率的主要原因。受伤大脑中星形胶质细胞的过度激活和炎症反应的过度表达是 TBI 的典型病理特征。罗格列酮 (ROS) 是一种过氧化物酶体增殖物激活受体-γ (PPAR-γ) 激动剂，以其抗炎活性而闻名。然而，ROS 治疗中涉及的炎症反应与星形胶质细胞 A1 极化之间的关系仍不清楚。本研究旨在探讨 ROS 治疗是否改善 TBI 后诱导的功能障碍和星形胶质细胞极化，并阐明这些功能的潜在机制。 SD大鼠随机分为假手术组、TBI组、TBI+ROS组、TBI+PPAR-γ拮抗剂组（GW9662+TBI）。采用CCI法制备大鼠TBI损伤模型；脑含水量测试和握线测试分数提示预后； FJB染色显示ROS对皮质损伤周围区神经元形态和数量的变化； ELISA、免疫荧光染色和蛋白质印迹分析揭示了TBI后ROS对炎症反应和星形胶质细胞活化的影响以及A1极化程度。 TBI组脑含水量、炎症因子表达量、星形胶质细胞活化程度均高于假手术组（P < 0.05）；与TBI组比较，ROS组上述指标表达量显着降低（P < 0.05）。与TBI组比较，ROS组PPAR-γ含量显着升高，C3含量显着降低（P < 0.05）；与TBI组相比，抑制剂组PPAR-γ含量显着降低，C3含量显着升高（P < 0.05）。 ROS可以在TBI后脑内炎症因子和星形胶质细胞活化减少的基础上，通过PPAR-γ途径抑制星形胶质细胞A1极化，从而发挥神经保护作用。