β-Hydroxybutyric acid (BHBA) reportedly has neuroprotective and anti-oxidation properties. The present study aimed to investigate the protective effects of BHBA against epilepsy. C57BL/6 J mice were exposed to lithium chloride and pilocarpine to induce epilepsy and then were administrated with 300 mg/kg/day BHBA for 30 days. The learning impairment was evaluated via Morris Water Maze. Neuron loss and cell apoptosis were detected through Nissl staining and TUNEL staining. The levels of oxidative stress-related factors were determined by commercial kits. The protein expression levels of AMP-activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor alpha (PPARα), anti-apoptotic Bcl-2, and pro-apoptotic Bax were measured through Western blots. It was found BHBA improved epilepsy- caused learning deficiency and attenuated epilepsy-mediated neuron loss and cell apoptosis in the hippocampus. BHBA ameliorated oxidative stress via decreasing the levels of reactive oxygen species and malondialdehyde plus strengthening the activities of glutathione peroxidase and superoxide dismutase. BHBA also promoted the phosphorylation of AMPK and upregulated PPARα in the epileptic hippocampus. In conclusion, BHBA attenuates neuronal damage in epileptic mice, which is associated with its anti-apoptotic and anti-oxidative effects as well as the activation of AMPK and PPARα.

中文翻译：

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β-羟基丁酸可减轻癫痫小鼠的神经元损伤。

据报道，β-羟基丁酸（BHBA）具有神经保护和抗氧化特性。本研究旨在调查BHBA对癫痫的保护作用。将C57BL / 6 J小鼠暴露于氯化锂和毛果芸香碱以诱发癫痫，然后以300 mg / kg / day BHBA给药30天。通过莫里斯水迷宫评估学习障碍。通过Nissl染色和TUNEL染色检测神经元丢失和细胞凋亡。氧化应激相关因子的水平通过商业试剂盒确定。通过蛋白质印迹法测量AMP激活的蛋白激酶（AMPK），p-AMPK，过氧化物酶体增殖物激活的受体α（PPARα），抗凋亡Bcl-2和促凋亡Bax的蛋白表达水平。研究发现，BHBA改善了癫痫引起的学习缺陷，并减弱了癫痫介导的海马神经元丢失和细胞凋亡。BHBA通过降低活性氧和丙二醛的水平以及增强谷胱甘肽过氧化物酶和超氧化物歧化酶的活性来减轻氧化应激。BHBA还促进癫痫海马中AMPK的磷酸化并上调PPARα。总之，BHBA减轻了癫痫小鼠的神经元损伤，这与其抗凋亡和抗氧化作用以及AMPK和PPARα的激活有关。BHBA通过降低活性氧和丙二醛的水平以及增强谷胱甘肽过氧化物酶和超氧化物歧化酶的活性来减轻氧化应激。BHBA还促进癫痫海马中AMPK的磷酸化并上调PPARα。总之，BHBA减轻了癫痫小鼠的神经元损伤，这与其抗凋亡和抗氧化作用以及AMPK和PPARα的激活有关。BHBA通过降低活性氧和丙二醛的水平以及增强谷胱甘肽过氧化物酶和超氧化物歧化酶的活性来减轻氧化应激。BHBA还促进癫痫海马中AMPK的磷酸化并上调PPARα。总之，BHBA减轻了癫痫小鼠的神经元损伤，这与其抗凋亡和抗氧化作用以及AMPK和PPARα的激活有关。