Ischemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such reactive microglial is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia. Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury. Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.

中文翻译：

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mTORC1 的药理学抑制通过调节小胶质细胞反应性减少 MCAO 后的神经死亡和损伤体积

缺血性中风是一种突发的急性疾病，其特征是神经元死亡、反应性胶质细胞增生（反应性小胶质细胞和星形胶质细胞）增加以及严重的炎症过程。神经炎症是脑缺血后的早期事件，其中小胶质细胞起主导作用。反应性小胶质细胞涉及驱动多种表型的功能和形态变化。在这种情况下，破译这种反应性小胶质细胞背后的分子机制对于制定保护神经元和维持缺血后早期神经炎症影响的某些大脑功能的策略至关重要。在这里，我们使用急性期脑缺血小鼠模型研究了哺乳动物雷帕霉素靶点（mTOR）活性在小胶质细胞反应中的作用。我们还确定了在缺血性损伤前后施用雷帕霉素（一种 mTOR 抑制剂）的治疗相关性。我们的数据表明，在脑缺血诱导之前或之后施用雷帕霉素，可以通过减弱小胶质细胞反应来减少脑损伤和神经元损失的体积。因此，我们的研究结果表明，在缺血急性期对 mTORC1 进行药理学抑制可能提供一种替代策略，通过减弱相关的神经炎症来减少神经元损伤。