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益生菌补充剂对戊四氮诱导的大鼠癫痫发作的保护作用的电生理、组织病理学和生化评估。

Electrophysiological, histopathological, and biochemical evaluation of the protective effect of probiotic supplementation against pentylenetetrazole-induced seizures in rats.

作者信息

Aygun Hatice, Akin Ali Tuğrul, Kızılaslan Nildem, Sumbul Orhan, Karabulut Derya

机构信息

Department of Physiology, Faculty of Medicine, University of Tokat Gaziosmanpasa, Tokat, Turkey.

Department of Biology, Faculty of Science and Literature, University of Erciyes, Kayseri, Turkey.

出版信息

Eur J Neurol. 2023 Nov;30(11):3540-3550. doi: 10.1111/ene.15359. Epub 2022 Apr 29.

DOI:10.1111/ene.15359
PMID:35429204
Abstract

BACKGROUND AND PURPOSE

Research on the relationship between the gut microbiome and epilepsy is accumulating. The present study was conducted to evaluate the effect of probiotic supplementation on pentylenetetrazole (PTZ)-induced seizures in rats.

METHODS

Twenty-one adult male Wistar albino rats were included. The animals were divided into three groups of seven rats. Group 1 was a control group, whereas Group 2 rats received PTZ treatment and Group 3 rats had PTZ+PB (probiotic) treatment. For 6 weeks, Groups 1 and 2 were given saline (1 ml), whereas Group 3 had probiotic supplement. In the 5th week, tripolar electrodes were attached to the rats. Electrophysiological, behavioral, biochemical, and immunohistochemical evaluations were performed in the 6 weeks after the treatment.

RESULTS

PB treatment significantly reduced seizures. In the PTZ group, expression levels of brain-derived neurotrophic factor, nerve growth factor (NGF), and Sox2 (SRY sex-determining region Y-box 2) in rat brains decreased significantly compared to the control group, whereas the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), total oxidant status (TOS), and nitric oxide (NO) levels increased. In the PTZ+PB group, NGF expression increased significantly compared to the PTZ group, whereas TNF-α, IL-6, TOS, and NO levels decreased. In histopathological examination, an abundance of necrotic neurons was notable in the PTZ group, which was less in the PTZ+PB group. In addition, body weight of the group supplemented with probiotics decreased after the treatment.

CONCLUSIONS

Our results suggest that probiotic supplementation may alleviate seizure severity and exert neuroprotective effects by reducing neuroinflammation and oxidative stress and altering the expression of neurotrophins in epileptogenic brains.

摘要

背景与目的

关于肠道微生物群与癫痫之间关系的研究正在不断积累。本研究旨在评估补充益生菌对戊四氮(PTZ)诱导的大鼠癫痫发作的影响。

方法

纳入21只成年雄性Wistar白化大鼠。将动物分为三组,每组7只。第1组为对照组,第2组大鼠接受PTZ治疗,第3组大鼠接受PTZ+PB(益生菌)治疗。6周内,第1组和第2组给予生理盐水(1毫升),而第3组给予益生菌补充剂。在第5周,将三极电极连接到大鼠身上。在治疗后的6周内进行电生理、行为、生化和免疫组化评估。

结果

PB治疗显著减少了癫痫发作。在PTZ组中,与对照组相比,大鼠脑中脑源性神经营养因子、神经生长因子(NGF)和Sox2(SRY性别决定区Y盒2)的表达水平显著降低,而肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、总氧化状态(TOS)和一氧化氮(NO)水平升高。在PTZ+PB组中,与PTZ组相比,NGF表达显著增加,而TNF-α、IL-6、TOS和NO水平降低。在组织病理学检查中,PTZ组可见大量坏死神经元,PTZ+PB组则较少。此外,补充益生菌组的大鼠体重在治疗后下降。

结论

我们的结果表明,补充益生菌可能减轻癫痫发作严重程度,并通过减少神经炎症和氧化应激以及改变致痫脑中神经营养因子的表达发挥神经保护作用。

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