Traumatic brain injury (TBI) causes substantial mortality and long-term disability worldwide. TGFβ1 is a unique molecular and functional signature in microglia, but the role of TGFβ1 in TBI is not clear. The purpose of this study was to investigate the role of TGFβ1 in TBI. The weight dropping device was used to establish TBI model of rats. Hematoxylin eosin staining and Bielschowsky silver staining were used to assess tissue loss. Beam walking and muscle strength tests were used to assess neurological deficits. Immunohistochemical staining was used to assess axonal injures. Western blotting was used to detect expression of related proteins. RT-PCR was used to detect expression of cytokines. Immunofluorescence staining was used to assess the microglia/macrophages activation. We observed obvious axonal injury and microglia/macrophages activation in the peri-lesion cortex. The expression of inflammatory cytokines was markedly high after TBI. The expression of TGFβ1 and TGFβRI were significantly reduced after TBI. TGFβ1 promoted the functional recovery and alleviated axonal injury 1 day after TBI. TGFβ1 promoted microglia/macrophages polarizing to alternative activation and alleviated neuroinflammation. These effects of TGFβ1 could be inhibited by LY2109761, the inhibitor of TGFRI/II. These results suggested that TGFβ1 played a protective role in axonal injury and could be a potential therapeutic target in early stages following TBI.

中文翻译：

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TGFβ1通过调节创伤性脑损伤中的小胶质细胞/巨噬细胞替代激活来减轻轴突损伤。

创伤性脑损伤 (TBI) 在世界范围内导致大量死亡率和长期残疾。TGFβ1 是小胶质细胞中独特的分子和功能特征，但 TGFβ1 在 TBI 中的作用尚不清楚。本研究的目的是研究 TGFβ1 在 TBI 中的作用。使用减重器建立大鼠TBI模型。苏木精伊红染色和 Bielschowsky 银染色用于评估组织损失。横梁行走和肌肉力量测试用于评估神经功能缺损。免疫组织化学染色用于评估轴突损伤。Western印迹用于检测相关蛋白的表达。RT-PCR用于检测细胞因子的表达。免疫荧光染色用于评估小胶质细胞/巨噬细胞活化。我们在病灶周围的皮层观察到明显的轴突损伤和小胶质细胞/巨噬细胞活化。TBI后炎性细胞因子的表达显着升高。TBI后TGFβ1和TGFβRI的表达显着降低。TGFβ1在TBI后1天促进功能恢复并减轻轴突损伤。TGFβ1 促进小胶质细胞/巨噬细胞极化至替代激活并减轻神经炎症。TGFβ1 的这些作用可以被 TGFRI/II 抑制剂 LY2109761 抑制。这些结果表明 TGFβ1 在轴突损伤中发挥保护作用，可能是 TBI 后早期的潜在治疗靶点。TGFβ1在TBI后1天促进功能恢复并减轻轴突损伤。TGFβ1 促进小胶质细胞/巨噬细胞极化至替代激活并减轻神经炎症。TGFβ1 的这些作用可以被 TGFRI/II 抑制剂 LY2109761 抑制。这些结果表明 TGFβ1 在轴突损伤中发挥保护作用，可能是 TBI 后早期的潜在治疗靶点。TGFβ1在TBI后1天促进功能恢复并减轻轴突损伤。TGFβ1 促进小胶质细胞/巨噬细胞极化至替代激活并减轻神经炎症。TGFβ1 的这些作用可以被 TGFRI/II 抑制剂 LY2109761 抑制。这些结果表明 TGFβ1 在轴突损伤中发挥保护作用，可能是 TBI 后早期的潜在治疗靶点。