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阿那白滞素、拉莫三嗪及其联合应用对锂-匹罗卡品大鼠颞叶癫痫模型的抗癫痫作用。

Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium-Pilocarpine Model of Temporal Lobe Epilepsy in Rats.

机构信息

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, Russia.

出版信息

Int J Mol Sci. 2023 Oct 20;24(20):15400. doi: 10.3390/ijms242015400.

Abstract

Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no preventive therapy for epilepsy is currently available. The purpose of this study was to evaluate the effects of anakinra, lamotrigine, and their combination on epileptogenesis using the rat lithium-pilocarpine model of temporal lobe epilepsy. The study showed that there was no significant difference in the number and duration of seizures between treated and untreated animals. However, the severity of seizures was significantly reduced after treatment. Anakinra and lamotrigine, alone or in combination, significantly reduced neuronal loss in the CA1 hippocampus compared to the control group. However, the drugs administered alone were found to be more effective in preventing neuron loss in the hippocampal CA3 field compared to combination treatment. The treatment alleviated the impairments in activity level, exploratory behavior, and anxiety but had a relatively weak effect on TLE-induced impairments in social behavior and memory. The efficacy of the combination treatment did not differ from that of anakinra and lamotrigine monotherapy. These findings suggest that anakinra and lamotrigine, either alone or in combination, may be clinically useful in preventing the development of histopathological and behavioral abnormalities associated with epilepsy.

摘要

颞叶癫痫是一种常见的慢性疾病,具有自发性癫痫发作,往往对药物治疗有抗性。颞叶癫痫的一个潜在原因是原发性脑损伤,因此预防初始事件后的癫痫发生是治疗的最佳方法。尽管如此,目前尚无预防癫痫的治疗方法。本研究旨在使用锂-匹罗卡品大鼠颞叶癫痫模型评估阿那白滞素、拉莫三嗪及其组合对癫痫发生的影响。研究表明,治疗组和未治疗组动物的癫痫发作次数和持续时间没有显著差异。然而,治疗后癫痫发作的严重程度显著降低。与对照组相比,阿那白滞素和拉莫三嗪单独或联合使用可显著减少 CA1 海马区的神经元丢失。然而,与联合治疗相比,单独给药的药物在预防海马 CA3 区神经元丢失方面更有效。治疗缓解了活动水平、探索行为和焦虑方面的损伤,但对 TLE 引起的社会行为和记忆损伤的影响相对较弱。联合治疗的疗效与阿那白滞素和拉莫三嗪单药治疗无差异。这些发现表明,阿那白滞素和拉莫三嗪单独或联合使用可能在预防与癫痫相关的组织病理学和行为异常方面具有临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/10607594/cce40c332d07/ijms-24-15400-g001.jpg

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