Abstract：
BACKGROUND: Status epilepticus (SE) as a severe neurodegenerative disease, greatly negatively affects people\'s health, and there is an urgent need for innovative treatments. The valuable neuroprotective effects of glucagon-like peptide-1 (GLP-1) in several neurodegenerative diseases have raised motivation to investigate the dipeptidyl peptidase-4 (DPP-4) inhibitor; alogliptin (ALO), an oral antidiabetic drug as a potential treatment for SE. ALO has shown promising neuroprotective effects in Alzheimer\'s and Parkinson\'s diseases, but its impact on SE has not yet been studied.
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.
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.
摘要：
背景：癫痫持续状态（SE）是一种严重的神经退行性疾病，极大地影响人们的健康，迫切需要创新的治疗方法。胰高血糖素样肽-1（GLP-1）在几种神经退行性疾病中有价值的神经保护作用，提高了研究二肽基肽酶-4（DPP-4）抑制剂的动机；阿格列汀（ALO），口服抗糖尿病药物作为SE的潜在治疗。ALO在阿尔茨海默病和帕金森病中显示出有希望的神经保护作用，但其对SE的影响尚未研究。
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。
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。
