Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: Impact on oxidative, inflammatory and apoptotic machineries
Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: Impact on oxidative, inflammatory and apoptotic machineries
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DOI：
10.1016/j.bcp.2018.09.004
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发表时间：
2018-10-01
影响因子：
5.8
通讯作者：
Azab, Samar S.
中科院分区：
文献类型：
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作者：
Ali, Alaa E.;Mandy, Heba M.;Azab, Samar S.
癫痫是细菌性脑膜炎的严重神经系统后遗症之一。利福平是一种众所周知的广谱抗生素，临床上用于脑膜炎的化学预防。除了抗生素作用外，利福平在各种神经系统疾病的实验模型中已被证明是一种有效的神经保护候选者。此外，利福平还具有抗氧化、抗炎和抗细胞凋亡的作用。本研究采用锂-匹罗卡平大鼠癫痫持续状态（SE）模型研究利福平在实验性脑膜炎剂量（20mg /kg, i.p）下的抗惊厥作用。此外，我们还研究了利福平对癫痫引起的组织病理学、神经化学和行为异常的影响。我们的研究表明，利福平预处理可减轻癫痫发作活动和由此产生的以苏木精和伊红为标志的海马损伤。在SE诱导24 h后，观察海马的氧化应激、神经炎症和细胞凋亡指标。我们发现利福平预处理抑制氧化应激，如正常化丙二醛和谷胱甘肽水平所示。利福平预处理可减轻硒诱导的神经炎症，降低海马白细胞介素-1 β、肿瘤坏死因子- α、核因子κ b和环氧化酶-2的表达。此外，利福平减轻硒诱导的神经元凋亡，这表明海马中细胞色素c免疫染色阳性细胞减少，caspase-3活性降低。此外，在SE诱导后第7天Morris水迷宫实验显示，利福平预处理可以改善认知功能障碍。因此，目前用于脑膜炎治疗的利福平具有改善其癫痫后遗症的潜在额外优势。
Epilepsy is one of the serious neurological sequelae of bacterial meningitis. Rifampicin, the well-known broad spectrum antibiotic, is clinically used for chemoprophylaxis of meningitis. Besides its antibiotic effects, rifampicin has been proven to be an effective neuroprotective candidate in various experimental models of neurological diseases. In addition, rifampicin was found to have promising antioxidant, anti-inflammatory and anti-apoptotic effects. Herein, we investigated the anticonvulsant effect of rifampicin at experimental meningitis dose (20 mg/kg, i.p.) using lithium-pilocarpine model of status epilepticus (SE) in rats. Additionally, we studied the effect of rifampicin on seizure induced histopathological, neurochemical and behavioral abnormalities. Our study showed that rifampicin pretreatment attenuated seizure activity and the resulting hippocampal insults marked by hematoxylin and eosin. Markers of oxidative stress, neuroinflammation and apoptosis were evaluated, in the hippocampus, 24 h after SE induction. We found that rifampicin pretreatment suppressed oxidative stress as indicated by normalized malondialdehyde and glutathione levels. Rifampicin pretreatment attenuated SE-induced neuroinflammation and decreased the hippocampal expression of interleukin-1 beta, tumor necrosis factor-alpha, nuclear factor kappa-B, and cyclooxygenase-2. Moreover, rifampicin mitigated SE-induced neuronal apoptosis as indicated by fewer positive cytochrome c immunostained cells and lower caspase-3 activity in the hippocampus. Furthermore, Morris water maze testing at 7 days after SE induction showed that rifampicin pretreatment can improve cognitive dysfunction. Therefore, rifampicin, currently used in the management of meningitis, has a potential additional advantage of ameliorating its epileptic sequelae.