依维莫司在大鼠脑出血模型中的神经保护作用及其可能机制。

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-09-25 DOI:10.1007/s10571-023-01409-6
Shima Shirzad, Farzaneh Vafaee, Fatemeh Forouzanfar
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引用次数: 0

摘要

哺乳动物雷帕霉素靶点(mTOR)是细胞生长和稳态的中心调节因子。mTOR活性的变化经常在许多神经系统疾病中观察到,如中风。脑出血(ICH)具有较高的死亡率和发病率。然而,目前还没有任何治疗方法能够提高脑出血后的疗效,因此迫切需要新的治疗方法。在本研究中,应用选择性mTOR抑制剂依维莫司来研究ICH后的结果和可能的潜在机制。通过自体血注射建立脑出血模型。术后连续14天腹膜内给药依维莫司(50和100µg/kg)。在ICH后3、7和14天检查神经功能。采集脑组织样本进行组织病理学和免疫组织化学(NF-k阳性细胞)检查。此外,纹状体用于评估与氧化应激相关的参数(超氧化物歧化酶(SOD)活性、丙二醛(MDA)和总硫醇水平)和炎症标志物(TNF-α和NO)。依维莫司改善脑出血引起的神经功能缺损。此外,与ICH组相比,依维莫司治疗减少了梗死体积和NF-β阳性细胞。此外,与ICH组相比,依维莫司显著增加了总硫醇含量和SOD活性,同时显著降低了MDA、NO和TNF-水平。总之,我们的研究表明依维莫司可以改善脑出血的预后,并调节脑出血后的氧化应激和炎症。雷帕霉素治疗降低了大鼠脑出血模型的神经功能缺陷、氧化应激和炎症。
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The Neuroprotective Effects and Probable Mechanisms of Everolimus in a Rat Model of Intracerebral Hemorrhage.

Mammalian target of rapamycin (mTOR) is a central regulator of cellular growth and homeostasis. Changes in mTOR activity are often observed in many neurological diseases, such as stroke. Intracerebral hemorrhage (ICH) is associated with high mortality and morbidity. However, there are currently no treatments that have been shown to enhance outcomes following ICH, so new treatments are urgently required. In this study, a selective mTOR inhibitor, everolimus, was applied to investigate the outcome after ICH and the possible underlying mechanism. The ICH model was established by autologous blood injection. Everolimus (50 and 100 µg/kg) was administered intraperitoneally for 14 consecutive days' post-operation. The neurological functions were examined at 3, 7, and 14 days' post-ICH. Samples of brain tissue were collected to perform histopathological and immunohistochemical (NF-k-positive cell) examinations. Besides, the striatum was used to evaluate parameters related to oxidative stress (superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol levels) and inflammation markers (TNF-α and NO). Everolimus ameliorated ICH-induced neurological deficits. In addition, treatment with everolimus reduced infarct volume and NF-k-β positive cells as compared to the ICH group. Furthermore, everolimus significantly increased total thiol content and SOD activity while significantly reducing MDA, NO, and TNF- levels as compared to the ICH group. Collectively, our investigation showed that everolimus improves ICH outcome and modulates oxidative stress and inflammation after ICH. Treatment with rapamycin reduced neurological deficient, oxidative stress, and inflammation in a rat model of intracerebral hemorrhage.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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