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益生菌与左乙拉西坦联合使用可增强实验性创伤后癫痫模型的抗癫痫疗效。

Probiotics Co-administered with LCM Enhance Antiepileptic Efficacy in the Experimental Post-traumatic Epilepsy Model.

作者信息

Aykin Ugur, Demirtas Cumaali, Uzun Sezin Kiroglu, Yildirim Mehmet

机构信息

Department of Physiology, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul, Turkey.

出版信息

Neurochem Res. 2025 Sep 6;50(5):290. doi: 10.1007/s11064-025-04541-5.

Abstract

The aim of the presented study was to investigate the effects of prebiotic inulin, probiotic VSL#3 (mixture of bacteria from 7 different species and 8 strains) and synbiotic (inulin + VSL#3) supplements applied together with lacosamide (LCM) on post-traumatic epilepsy (PTE). In addition, effectiveness of the relevant treatments on comorbid problems related to learning and memory, anxiety, motor performance and pain threshold that may develop together with seizures due to traumatic brain injury (TBI) and PTE was also examined using behavioral tests. In experiments, adult male Sprague-Dawley rats, divided into 6 groups, were given 30 mg/kg LCM or 1000 mg/kg inulin together with LCM as prebiotic, VSL#3 mixture containing 10 × 10 CFU/kg bacterial colonies as probiotic and (inulin + VSL#3) as synbiotic for 28 days by oral gavage after mild-TBI was induced by weight-drop method and electroencephalogram electrodes were placed. In order to reveal the tendency to trauma-induced seizures, PTE was modeled by injection of 30 + 15 + 15 mg/kg pentylenetetrazole at subconvulsant doses at 30-min intervals on 7th, 14th, 21st and 28th days after TBI and seizures were scored according to Racine scale. Locomotor, cognitive and pain-related behaviors of animals other than seizures were also examined using open field, rotarod, elevated plus maze, radial arm maze, dynamic plantar and thermal plantar tests. It was determined that LCM applied alone was effective in seizure control related to PTE, but probiotic supplement in form of LCM + VSL#3 provided more effective seizure control. In addition, it was determined that probiotic VSL#3 applied together with LCM increased locomotor activity, both VSL#3 and inulin prevented the disorder in forced motor activity caused by LCM, and VSL#3 + inulin applied together with LCM increased mechanical pain threshold. It was concluded that probiotic VSL#3 combined with antiepileptic LCM provides more effective seizure control by strengthening the antiepileptic activity of LCM in management of PTE.

摘要

本研究的目的是调查益生元菊粉、益生菌VSL#3(7种不同菌种和8个菌株的细菌混合物)以及与拉科酰胺(LCM)联合使用的合生元(菊粉 + VSL#3)补充剂对创伤后癫痫(PTE)的影响。此外,还通过行为测试检查了相关治疗对因创伤性脑损伤(TBI)和PTE引起的癫痫发作可能同时出现的与学习和记忆、焦虑、运动表现及疼痛阈值相关的共病问题的有效性。在实验中,将成年雄性Sprague-Dawley大鼠分为6组,在通过重物坠落法诱导轻度TBI并放置脑电图电极后,通过口服灌胃给予30 mg/kg LCM或与LCM一起给予1000 mg/kg菊粉作为益生元、含有10×10 CFU/kg菌落的VSL#3混合物作为益生菌以及(菊粉 + VSL#3)作为合生元,持续28天。为了揭示创伤性癫痫发作的倾向,在TBI后第7、14、21和28天,以亚惊厥剂量每隔30分钟注射30 + 15 + 15 mg/kg戊四氮来模拟PTE,并根据Racine量表对癫痫发作进行评分。还使用旷场试验、转棒试验、高架十字迷宫试验、放射状臂迷宫试验、动态足底试验和热足底试验检查了动物除癫痫发作外的运动、认知和疼痛相关行为。结果确定,单独使用LCM对与PTE相关的癫痫控制有效,但LCM + VSL#3形式的益生菌补充剂能提供更有效的癫痫控制。此外,还确定与LCM联合使用的益生菌VSL#3增加了运动活动,VSL#3和菊粉均预防了LCM引起的强迫运动活动障碍,并且与LCM联合使用的VSL#3 +菊粉提高了机械性疼痛阈值。得出的结论是,益生菌VSL#3与抗癫痫药物LCM联合使用,通过增强LCM在PTE管理中的抗癫痫活性,能提供更有效的癫痫控制。

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