Abstract：
Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.
摘要：
戊四唑（PTZ）诱导的点燃是一种广泛使用的实验模型，用于评估抗癫痫药物及其新型组合对癫痫发作进展的影响。本研究旨在评估伊维菌素（IVM）和rufinamide（RUFI）单独及其与维生素E的组合的抗点燃作用。对小鼠进行了11次PTZ（40mg/kg）注射，然后评估焦虑样行为和认知能力在一系列行为测试中，随后进行大脑分离以进行生化和组织病理学评估。结果显示IVM+RUFI(P<0.001)对点燃进展有明显的保护作用，焦虑样行为和认知缺陷。然而,补充维生素E的效果优于二重奏疗法，因为这些小鼠被认为是最无所畏惧的开放访问，开阔场地的照明和高架区域，亮/暗和高架迷宫（P<0.0001）。Further,他们在y迷宫测试中表现出对熟悉环境的明显记忆（P<0.01）和新颖的异议识别（P<0.05）。此外,他们在莫里斯水迷宫中被动回避和空间记忆中对厌恶刺激的回忆是明显的(P<0.0001)，与点燃的老鼠相比。IVMRUFI二重奏疗法及其与维生素E的共同给药可预防点燃引发的大脑氧化应激和海马神经元损伤。我们得出的结论是，维生素E的共同给药的好处可能是维生素E的抗氧化和抗炎作用的结果，这可能增强了RUFI的抗癫痫作用和伊维菌素对GABA-A的调节潜力。
