The mammalian target of rapamycin (mTOR) was reported to regulate cell autophagy and outcomes of several neurological diseases. Mitochondria, which serve as critical organelles in neurons. are also involved in the pathology of neurological diseases. However, the role of mTOR in mitochondrial morphology has not been clarified especially in subarachnoid hemorrhage (SAH). In this study, we established SAH models both in vivo and in vitro. Rapamycin and 3-methyl adenine (3-MA) were then administered to alter mTOR activity. Post-SAH assessment included SAH grading, neurological evaluation, blood-brain barrier (BBB) permeability, brain water content, mitochondrial membrane potential (MMP), mitochondrial morphology, ATP content, cell viability, cytotoxicity, and expression of proteins related to apoptosis and mitochondrial fission. The results showed that (1) neurological deficits, BBB permeability, and brain edema were increased after SAH and that cell viability was exacerbated in brain tissue. (2) Excessive mitochondrial fission was evident based on changes in mitochondrial morphology, while MMP and ATP content were decreased in neurons after SAH. (3) Administration of rapamycin improved the excessive mitochondrial fission and restored mitochondrial function, which subsequently reduced apoptosis. (4) 3-MA showed an adverse effect on mitochondria and aggravated excessive mitochondrial fission and dysfunction in SAH. Neurological deficits and neuronal viability were also exacerbated following the administration of 3-MA. Therefore, our study suggests that mTOR inhibition has neuroprotective effects against neuronal injury after SAH via alleviating excessive mitochondrial fission.

中文翻译：

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mTOR的抑制通过减轻线粒体过度裂变减轻了蛛网膜下腔出血后的早期脑损伤。

据报道，雷帕霉素（mTOR）的哺乳动物靶标可调节细胞自噬和几种神经系统疾病的预后。线粒体是神经元中的关键细胞器。也参与神经系统疾病的病理学。但是，尚未明确mTOR在线粒体形态中的作用，尤其是在蛛网膜下腔出血（SAH）中。在这项研究中，我们建立了体内和体外的SAH模型。然后施用雷帕霉素和3-甲基腺嘌呤（3-MA）以改变mTOR活性。SAH后评估包括SAH分级，神经学评估，血脑屏障（BBB）通透性，脑水含量，线粒体膜电位（MMP），线粒体形态，ATP含量，细胞活力，细胞毒性以及与细胞凋亡和线粒体裂变。结果表明：（1）SAH后神经功能缺损，血脑屏障通透性和脑水肿增加，并且脑组织中的细胞活力加剧。（2）线粒体形态改变明显导致线粒体过度分裂，而SAH后神经元MMP和ATP含量降低。（3）雷帕霉素的给药改善了线粒体过度分裂，恢复了线粒体功能，从而减少了细胞凋亡。（4）3-MA对SAH的线粒体有不良影响，并加剧了线粒体的过度裂变和功能障碍。3-MA给药后神经功能缺损和神经元生存能力也加剧。因此，