The Second Hospital of Hebei Medical University, China.
The Fourth Hospital of Shijiazhuang, China.
Folia Neuropathol. 2022;60(2):153-164. doi: 10.5114/fn.2022.118184.
Accumulating studies have demonstrated that neuronal autophagy and inflammation are crucial for hippocampus development in rats subjected to traumatic brain injury (TBI). Therefore, we have investigated whether resveratrol is protective against brain damage through the attenuation of neuronal autophagy and inflammation, and explored underlying mechanisms.
Rats were injected with resveratrol (50 mg/kg, i.p.), following controlled cortical impact (CCI) injury. Brain water content, behavioral studies, and mNSS score were measured to assess the effects of resveratrol treatment. Autophagy-related proteins and inflammatory cytokines in the hippocampus were detected by Western blotting at 12, 24, and 48 hours after TBI. In addition, spatial distribution of LC3 was evaluated with immunofluorescence analysis 24 hours after injury. Finally, factors related to PI3K/Akt/mTOR signaling pathway were assessed at the same time in the hippocampus.
Our results depicted that resveratrol could reduce the cerebral edema caused by TBI and improve the recovery of functional deficits in rats. Resveratrol was also able to remarkably reduce the expression of LC3 II and Beclin-1, while increased the expression levels of P62 in the hippocampus. Moreover, we found that interleukin b (IL-1b) and tumor necrosis factor a (TNF-a) were significantly decreased in resveratrol-treated rats. Indeed, we observed an activation of the PI3K/Akt/mTOR pathway after TBI, which may be related to the neuro-protective effect of resveratrol.
Data presented herein support that resveratrol is a potential treatment against TBI through the inhibition of neuronal autophagy and inflammation by activation of PI3K/Akt/mTOR pathway.
越来越多的研究表明，神经元自噬和炎症对于创伤性脑损伤（TBI）大鼠海马体的发育至关重要。因此，我们研究了白藜芦醇是否通过抑制神经元自噬和炎症来发挥其对脑损伤的保护作用，并探讨了其潜在机制。
在控制性皮质撞击（CCI）损伤后，大鼠腹腔内注射白藜芦醇（50mg/kg）。通过测量脑水含量、行为学研究和 mNSS 评分来评估白藜芦醇治疗的效果。在 TBI 后 12、24 和 48 小时，通过 Western blot 检测海马体中的自噬相关蛋白和炎症细胞因子。此外，在损伤后 24 小时通过免疫荧光分析评估 LC3 的空间分布。最后，同时在海马体中评估与 PI3K/Akt/mTOR 信号通路相关的因素。
我们的结果表明，白藜芦醇可以减轻 TBI 引起的脑水肿，并改善大鼠功能缺陷的恢复。白藜芦醇还可以显著降低 LC3 II 和 Beclin-1 的表达，同时增加 P62 的表达水平。此外，我们发现白藜芦醇治疗组大鼠海马体中的白细胞介素 b（IL-1b）和肿瘤坏死因子 a（TNF-a）显著减少。事实上，我们观察到 TBI 后 PI3K/Akt/mTOR 通路的激活，这可能与白藜芦醇的神经保护作用有关。
本文的数据支持白藜芦醇通过激活 PI3K/Akt/mTOR 通路抑制神经元自噬和炎症，是一种治疗 TBI 的潜在药物。
