Postconditioning has been shown to protect the mouse brain from ischemic injury. However, the neuroprotective mechanisms of postconditioning remain elusive. We have found that toll-like receptor 5 (TLR5) plays an integral role in postconditioning-induced neuroprotection through Akt/nuclear factor kappa B (NF-κB) activation in cerebral ischemia. Compared to animals that received 30 min of transient middle cerebral artery occlusion (tMCAO) group, animals that also underwent postconditioning showed a significant reduction of up to 60.51% in infarct volume. Postconditioning increased phospho-Akt (p-Akt) levels and NF-κB translocation to the nucleus as early as 1 h after tMCAO and oxygen-glucose deprivation. Furthermore, inhibition of Akt by Akt inhibitor IV decreased NF-κB promoter activity after postconditioning. Immunoprecipitation showed that interactions between TLR5, MyD88, and p-Akt were increased from postconditioning both in vivo and in vitro. Similar to postconditioning, flagellin, an agonist of TLR5, increased NF-κB nuclear translocation and Akt phosphorylation. Our results suggest that postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathways via TLR5 after cerebral ischemia. Additionally, the TLR5 agonist flagellin can simulate the neuroprotective mechanism of postconditioning in cerebral ischemia.

中文翻译：

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通过NF-κB激活TLR5是小鼠脑缺血后调节的神经保护机制。

已显示后处理可保护小鼠大脑免受缺血性损伤。但是，后处理的神经保护机制仍然难以捉摸。我们发现，在脑缺血中，Akt /核因子κB（NF-κB）激活后，toll​​样受体5（TLR5）在后处理诱导的神经保护中起着不可或缺的作用。与接受短暂脑中动脉闭塞30分钟（tMCAO）组的动物相比，也经过后处理的动物显示梗塞体积最多可明显减少60.51％。早在tMCAO和氧葡萄糖剥夺后1小时，后处理会增加磷酸化Akt（p-Akt）水平和NF-κB易位至核。此外，Akt抑制剂IV对Akt的抑制作用会降低后处理后的NF-κB启动子活性。体内和体外。与后处理类似，鞭毛蛋白是TLR5的激动剂，可增加NF-κB核易位和Akt磷酸化。我们的结果表明，后处理具有通过脑缺血后TLR5激活NF-κB和Akt生存途径的神经保护作用。此外，TLR5激动剂鞭毛蛋白可以模拟脑缺血后适应的神经保护机制。