The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood–brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1β, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.

中文翻译：

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肝素修饰的超顺磁性氧化铁纳米颗粒通过减轻炎症和氧化应激来抑制氯化锂/毛果芸香碱诱导的大鼠颞叶癫痫

抗癫痫药物的研发仍然是一个漫长的过程。本研究制备了肝素修饰的超顺磁性氧化铁纳米粒子（UFH-SPIONs），并研究了其抗癫痫作用和潜在机制。 UFH-SPION 是稳定、均质的纳米系统，具有抗氧化酶活性，能够穿过血脑屏障 (BBB) 并富含海马致癫痫病灶。 UFH-SPIONs 预处理可有效延长锂/毛果芸香碱 (LP) 诱导大鼠癫痫发作后的癫痫发作时间并降低癫痫发作严重程度。 UFH-SPIONs预处理显着降低了海马组织中炎症因子的表达，包括IL-6、IL-1β和TNF-α。在用 UFH-SPION 预处理后，LP 诱导的海马组织氧化应激反过来减少，抗氧化酶超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 水平增加以及脂质过氧化水平降低证明了这一点（MDA）。此外，用 UFH-SPION 预处理后，LP 诱导的凋亡细胞上调有所减少。总之，这些观察结果表明，UFH-SPION 预处理可改善 LP 诱导的癫痫发作，并下调炎症反应和氧化应激，从而在癫痫期间发挥神经元保护作用。