OBJECTIVE: The present study aimed to explore the repurposing potential for ALO in a lithium/pilocarpine (Li/Pil)-induced SE model in rats.
METHODS: ALO (30 mg/kg/day) was administered via gavage for 14 days, and SE was subsequently induced in the rats using a single dose of Li/Pil (127/60 mg/kg), while levetiracetam was used as a standard antiepileptic drug.
RESULTS: The results showed that ALO reduced seizure severity and associated hippocampal neurodegeneration. ALO also increased γ-aminobutyric acid (GABA) levels, diminished glutamate spikes, and corrected glial fibrillary acidic protein (GFAP) changes. At the molecular level, ALO increased GLP-1 levels and activated its downstream signaling pathway, AMP-activated protein kinase (AMPK)/sirtuin-1 (SIRT1). ALO also dampened the brain\'s pro-oxidant response, curbed neuroinflammation, and counteracted hippocampal apoptosis affording neuroprotection. In addition, it activated autophagy as indicated by Beclin1 elevation.
CONCLUSIONS: This study suggested that the neuroprotective properties and autophagy-enhancing effects of ALO make it a promising treatment for SE and can potentially be used as a management approach for this condition.
目的:本研究旨在探讨ALO在锂/毛果芸香碱(Li/Pil)诱导的大鼠SE模型中的再利用潜力。
方法:ALO(30mg/kg/天)通过灌胃给药14天,随后,使用单剂量的Li/Pil(127/60mg/kg)在大鼠中诱导SE,而左乙拉西坦用作标准抗癫痫药物。
结果:结果显示ALO降低了癫痫发作的严重程度和相关的海马神经变性。ALO还增加了γ-氨基丁酸(GABA)水平,谷氨酸尖峰减少,并纠正胶质纤维酸性蛋白(GFAP)的变化。在分子水平上,ALO增加GLP-1水平并激活其下游信号通路,AMP激活蛋白激酶(AMPK)/沉默调节蛋白-1(SIRT1)。ALO还抑制了大脑的促氧化反应,遏制神经炎症,并抵消海马细胞凋亡,提供神经保护作用。此外,如Beclin1升高所示,它激活了自噬。
结论:这项研究表明,ALO的神经保护特性和自噬增强作用使其成为SE的有希望的治疗方法,并可能用作这种疾病的管理方法。