Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy.
Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy.
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DOI：
10.1016/j.expneurol.2015.06.012
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发表时间：
2015-09
影响因子：
5.3
通讯作者：
Patel M
中科院分区：
文献类型：
--
作者：
Bhuyan P;Patel DC;Wilcox KS;Patel M
颞叶癫痫（TLE）是获得性癫痫的最常见形式，可由包括病毒感染在内的几种煽动事件引起。然而，三分之一的TLE患者对目前的抗癫痫药物具有药物抗性，因此，迫切需要开发预防疾病发展的抗癫痫治疗。氧化应激和氧化还原改变是脑损伤的重要病因。本研究的目的是确定颞叶癫痫（TLE）的TMEV（泰勒鼠脑脊髓炎病毒）模型中是否发生氧化应激。C57 B1/6小鼠皮质内注射TMEV或PBS，观察急性癫痫发作。在TMEV注射后的不同时间点，分析了小牛的还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）和3-硝基酪氨酸（3 NT）水平。感染TMEV的小鼠在感染后第3天和第7天（dpi）之间表现出行为癫痫发作。癫痫发作的强度随时间推移而增加，大多数癫痫发作在注射后6天为Racine量表的4或5期。使用在观察期间表现出至少一次癫痫发作的小鼠进行生化分析。感染TMEV的小鼠在接种后3、4和14天的GSH水平显着下降伴随着GSSH水平的增加以及氧化还原状态的损害。此外，在这些时间点，TMEV感染的小鼠中3 NT水平显著增加。这些氧化还原的变化与急性癫痫发作的发生在这个模型中。有趣的是，我们在感染TMEV的小鼠的小脑中在3dpi没有看到任何指数的变化，这表明这些改变定位于海马体和可能的其他边缘区域。这是第一个研究，以证明发生氧化应激的TMEV模型感染诱导的TLE。在与急性行为性癫痫发作的出现相一致的时间点观察到氧化还原改变，这表明这些变化可能是癫痫发作活动的结果。我们的研究结果支持这一假设，即氧化还原变化与癫痫发作活动在获得性癫痫，无论煽动侮辱，并建议氧化应激作为一个潜在的治疗目标，为他们的治疗。
Temporal lobe epilepsy (TLE) is the most common form of acquired epilepsy that can be caused by several inciting events including viral infections. However, one-third of TLE patients are pharmacoresistant to current antiepileptic drugs and therefore, there is an urgent need to develop antiepileptogenic therapies that prevent the development of the disease. Oxidative stress and redox alterations have recently been recognized as important etiological factors contributing to seizure-induced neuronal damage. The goal of this study was to determine if oxidative stress occurs in the TMEV (Theiler’s murine encephalomyelitis virus) model of temporal lobe epilepsy (TLE). C57Bl/6 mice were injected with TMEV or with PBS intracortically and observed for acute seizures. At various time points after TMEV injection, hippocampi were analyzed for levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3-nitrotyrosine (3NT). Mice infected with TMEV displayed behavioral seizures between days 3 and 7 days post-infection (dpi). The intensity of seizures increased over time with most of the seizures being a stage 4 or 5 on the Racine scale at 6 days p.i. Mice exhibiting at least one seizure during the observation period were utilized for the biochemical analyses. The levels of GSH were significantly depleted in TMEV infected mice at 3, 4 and 14 days p.i. with a concomitant increase in GSSH levels as well as an impairment of the redox status. Additionally, there was a substantial increase in 3NT levels in TMEV infected mice at these time points. These redox changes correlated with the occurrence of acute seizures in this model. Interestingly, we did not see changes in any of the indices in the cerebellum of TMEV-infected mice at 3 dpi indicating that these alterations are localized to the hippocampus and perhaps other limbic regions. This is the first study to demonstrate the occurrence of oxidative stress in the TMEV model of infection-induced TLE. The redox alterations were observed at time points coinciding with the appearance of acute behavioral seizures suggesting that these changes might be a consequence of seizure activity. Our results support the hypothesis that redox changes correlate with seizure activity in acquired epilepsies, regardless of the inciting insults, and suggest oxidative stress as a potential therapeutic target for their treatment.