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Therapeutic effects of modafinil in ischemic stroke; possible role of NF-κB downregulation.
Immunopharmacology and Immunotoxicology ( IF 3.3 ) Pub Date : 2019-09-23 , DOI: 10.1080/08923973.2019.1669045
Hasan Yousefi-Manesh 1, 2, 3 , Amir Rashidian 1 , Sara Hemmati 1, 2 , Samira Shirooie 4 , Mohammad Amin Sadeghi 1, 2 , Nazanin Zarei 1, 2 , Ahmad Reza Dehpour 1, 2
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Background: The phenomenon of ischemic stroke receives maximal attention nowadays. Many studies are designed to discover new therapies for reducing debilitating consequences of this disorder. Development of stroke-related tissue damage is due to the combination of blood flow occlusion and reperfusion phase. Inflammatory pathways participate in excess oxidative stress formation after reperfusion. Modafinil is a well-known medication prescribed for sleep disorders. Recently, several studies have focused on finding new indications for modafinil treatment. Anti-inflammatory effects of modafinil through disrupting NF-κB signaling pathway is reported previously. Downregulation of inflammatory cytokines and further oxidative damage have also been mentioned in various experiments. So far, no specific experiment had been conducted to assess the anti-inflammatory effects of modafinil on ischemic stroke. Material and methods: We evaluated outcomes of acutely administered modafinil on post-stroke behaviors and histopathological features (including apoptotic caspase-3 expressing neurons) through bilateral common carotid artery occlusion in rats. Alterations in concentrations of TNFɑ and IL-1β were assessed, together with malon di-aldehyde (MDA) to represent oxidation level. Western blotting was used to reveal the involvement of NF-κB downregulation. Considering possible alterations in blood flow and neuronal metabolism, we also assessed the effects of modafinil on cerebral glucose metabolism through PET scan. Results and discussion: Modafinil exhibited promising effects on remission of behavioral deficits and the number of degenerated neurons in ischemic hippocampus CA1 region. IL-1β and MDA levels were downregulated in treated animals. However, no significant alteration was observed in PET results and TNFɑ between treated and non-treated ischemic brains. Decreased protein levels of NF-κB was also measured in modafinil treated animals. Conclusion: Our findings demonstrate a promising therapeutic effect of modafinil for animal models of stroke.

中文翻译:

莫达非尼对缺血性中风的治疗作用;NF-κB下调的可能作用。

背景:缺血性中风的现象引起了当今的最大关注。许多研究旨在发现新的疗法,以减少这种疾病的虚弱后果。与中风相关的组织损伤的发展是由于血流阻塞和再灌注阶段的结合。炎症途径参与再灌注后过量的氧化应激形成。莫达非尼(Modafinil)是治疗睡眠障碍的知名药物。最近,一些研究集中于寻找莫达非尼治疗的新适应症。莫达非尼通过破坏NF-κB信号通路的抗炎作用已有报道。在各种实验中也提到了炎性细胞因子的下调和进一步的氧化损伤。至今,没有进行具体实验来评估莫达非尼对缺血性中风的抗炎作用。材料和方法:我们通过大鼠双侧颈总动脉闭塞评估了莫达非尼对中风后行为和组织病理学特征(包括表达凋亡caspase-3的神经元)急性给药的结果。评估了TNFɑ和IL-1β的浓度变化以及丙二醛(MDA)代表氧化水平。Western印迹用于揭示NF-κB下调的参与。考虑到血流和神经元代谢的可能改变,我们还通过PET扫描评估了莫达非尼对脑葡萄糖代谢的影响。结果与讨论:莫达非尼对缓解行为缺陷和缺血性海马CA1区神经元数量的减少显示出有希望的效果。在治疗的动物中IL-1β和MDA水平下调。然而,在治疗和未治疗的缺血性脑之间,PET结果和TNFɑ均未观察到显着变化。在莫达非尼治疗的动物中,NF-κB的蛋白水平也降低了。结论:我们的发现证明莫达非尼对中风动物模型具有良好的治疗作用。
更新日期:2019-11-01
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