Introduction: Epilepsy is a chronic neurological condition characterized by behavioral, molecular, and neurochemical alterations. Current antiepileptic drugs are associated with various adverse impacts. The main goal of the current study is to investigate the possible anticonvulsant effect of selenium nanoparticles (SeNPs) against pentylenetetrazole (PTZ)-mediated epileptic seizures in mice hippocampus. Sodium valproate (VPA) was used as a standard anti-epileptic drug.
Methods: Mice were assigned into five groups (n=15): control, SeNPs (5 mg/kg, orally), PTZ (60 mg/kg, intraperitoneally), SeNPs+PTZ and VPA (200 mg/kg)+PTZ. All groups were treated for 10 days.
Results: PTZ injection triggered a state of oxidative stress in the hippocampal tissue as represented by the elevated lipoperoxidation, heat shock protein 70 level, and nitric oxide formation while decreased glutathione level and antioxidant enzymes activity. Additionally, the blotting analysis showed downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the epileptic mice. A state of neuroinflammation was recorded following the developed seizures represented by the increased pro-inflammatory cytokines. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions. At the neurochemical level, acetylcholinesterase activity and monoamines content were decreased in the epileptic mice, accompanied by high glutamate and low GABA levels in the hippocampal tissue. However, SeNP supplementation was found to delay the onset and decreased the duration of tonic, myoclonic, and generalized seizures following PTZ injection. Moreover, SeNPs were found to provide neuroprotection through preventing the development of oxidative challenge via the upregulation of Nrf2 and HO-1, inhibiting the inflammatory response and apoptotic cascade. Additionally, SeNPs reversed the changes in the activity and levels of neuromodulators following the development of epileptic seizures.
Conclusion: The obtained results suggest that SeNPs could be used as a promising anticonvulsant drug due to its potent antioxidant, anti-inflammatory, and neuromodulatory activities.

Keywords: epilepsy, selenium nanoparticles, oxidative stress, neuroinflammation and apoptosis, monoamines, GABA and glutamate


中文翻译：

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硒纳米粒子预处理逆转戊四唑诱导的小鼠癫痫发作中的行为、氧化损伤、神经元损失和神经化学改变。

简介：癫痫是一种以行为、分子和神经化学改变为特征的慢性神经系统疾病。目前的抗癫痫药物与各种不良影响有关。本研究的主要目的是研究硒纳米粒子 (SeNPs) 对戊四唑 (PTZ) 介导的小鼠海马癫痫发作可能的抗惊厥作用。丙戊酸钠（VPA）被用作标准的抗癫痫药物。
方法：将小鼠分为五组（n=15）：对照、SeNPs（5 mg/kg，口服）、PTZ（60 mg/kg，腹膜内）、SeNPs+PTZ 和 VPA（200 mg/kg）+PTZ。所有组均治疗10天。
结果：PTZ 注射在海马组织中引发了一种氧化应激状态，表现为脂过氧化、热休克蛋白 70 水平和一氧化氮形成升高，而谷胱甘肽水平和抗氧化酶活性降低。此外，印迹分析显示癫痫小鼠中核因子红细胞 2 相关因子 2 (Nrf2) 和血红素加氧酶-1 (HO-1) 下调。在以增加的促炎细胞因子为代表的癫痫发作后记录了神经炎症状态。此外，在癫痫性惊厥发展后记录了神经元凋亡。在神经化学水平上，癫痫小鼠的乙酰胆碱酯酶活性和单胺含量降低，同时海马组织中谷氨酸含量高，GABA含量低。然而，发现补充 SeNP 可延迟 PTZ 注射后的强直、肌阵挛和全身性癫痫发作的发作并缩短其持续时间。此外，SeNPs 被发现通过上调 Nrf2 和 HO-1 来防止氧化攻击的发展，抑制炎症反应和凋亡级联反应，从而提供神经保护。此外，SeNPs 逆转了癫痫发作发展后神经调节剂的活性和水平的变化。
结论：所获得的结果表明，SeNPs 可作为一种有前途的抗惊厥药物，因为它具有强大的抗氧化、抗炎和神经调节活性。

关键词：癫痫，硒纳米颗粒，氧化应激，神经炎症和细胞凋亡，单胺，GABA和谷氨酸