Japanese encephalitis virus , a neurotropic flavivirus, causes sporadic encephalitis with nearly 25% fatal case reports. JEV infects neural stem/progenitor cells (NSPCs) and decreases their proliferation. Statin, a commonly used class of cholesterol lowering drug, has been shown to possess potent anti-inflammatory and neuroprotective effects in acute brain injury and chronic neurodegenerative conditions. Here, we aimed to check the efficacy of atorvastatin in alleviating the symptoms of Japanese encephalitis (JE). Using BALB/c mouse model of JEV infection, we observed that atorvastatin effectively reduces viral load in the subventricular zone (SVZ) of infected pups and decreases the resultant cell death. Furthermore, atorvastatin abrogates microglial activation and production of proinflammatory cyto/chemokine production post JEV infection in vivo. It also reduced interferon-β response in the neurogenic environs. The neuroprotective role of atorvastatin is again evident from the rescued neurosphere size and decreased cell death in vitro . It has also been observed that upon atorvastatin administration, cell cycle regulatory proteins and cell survival proteins are also restored to their respective expression level as observed in uninfected animals. Thus the antiviral, immunomodulatory and neuroprotective roles of atorvastatin reflect in our experimental observations. Therefore, this drug broadens a path for future therapeutic measures against JEV infection.

中文翻译：

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阿托伐他汀改善日本脑炎实验模型中的病毒负荷和神经干/祖细胞 (NSPC) 死亡

日本脑炎病毒是一种嗜神经黄病毒，可引起散发性脑炎，有近 25% 的死亡病例报告。JEV 感染神经干/祖细胞 (NSPC) 并降低其增殖。他汀类药物是一种常用的降胆固醇药物，已被证明在急性脑损伤和慢性神经退行性疾病中具有有效的抗炎和神经保护作用。在这里，我们旨在检查阿托伐他汀在缓解日本脑炎 (JE) 症状方面的功效。使用 JEV 感染的 BALB/c 小鼠模型，我们观察到阿托伐他汀有效降低受感染幼崽脑室下区 (SVZ) 的病毒载量并减少由此产生的细胞死亡。此外，阿托伐他汀在体内抑制 JEV 感染后小胶质细胞的激活和促炎细胞/趋化因子的产生。它还降低了神经源性环境中的干扰素-β 反应。阿托伐他汀的神经保护作用再次从获救的神经球大小和体外细胞死亡减少中得到证明。还观察到在阿托伐他汀给药后，细胞周期调节蛋白和细胞存活蛋白也恢复到它们在未感染动物中观察到的各自表达水平。因此，阿托伐他汀的抗病毒、免疫调节和神经保护作用反映在我们的实验观察中。因此，这种药物为未来针对 JEV 感染的治疗措施拓宽了道路。还观察到在阿托伐他汀给药后，细胞周期调节蛋白和细胞存活蛋白也恢复到它们在未感染动物中观察到的各自表达水平。因此，阿托伐他汀的抗病毒、免疫调节和神经保护作用反映在我们的实验观察中。因此，这种药物为未来针对 JEV 感染的治疗措施拓宽了道路。还观察到在阿托伐他汀给药后，细胞周期调节蛋白和细胞存活蛋白也恢复到它们在未感染动物中观察到的各自表达水平。因此，阿托伐他汀的抗病毒、免疫调节和神经保护作用反映在我们的实验观察中。因此，这种药物为未来针对 JEV 感染的治疗措施拓宽了道路。