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海马低频刺激对点燃大鼠促炎因子及星形胶质细胞活性的长期影响

Long-Term Effects of Hippocampal Low-Frequency Stimulation on Pro-Inflammatory Factors and Astrocytes Activity in Kindled Rats.

作者信息

Rohani Razieh, Aliaghaei Abbas, Abdollahifar Mohammad-Amin, Sadeghi Yousef, Zare Leila, Dehghan Samaneh, Heidari Mohammad Hassan

机构信息

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences and Health Services (SBMU), Tehran, Iran.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Cell J. 2021 Apr;23(1):85-92. doi: 10.22074/cellj.2021.7139. Epub 2021 Mar 1.

DOI:10.22074/cellj.2021.7139
PMID:33650824
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7944118/
Abstract

OBJECTIVE

Epilepsy is accompanied by inflammation, and the anti-inflammatory agents may have anti-seizure effects. In this investigation, the effect of deep brain stimulation, as a potential therapeutic approach in epileptic patients, was investigated on seizure-induced inflammatory factors.

MATERIALS AND METHODS

In the present experimental study, rats were kindled by chronic administration of pentylenetetrazol (PTZ; 34 mg/Kg). The animals were divided into intact, sham, low-frequency deep brain stimulation (LFS), kindled, and kindled +LFS groups. In kindled+LFS and LFS groups, animals received four trains of intra-hippocampal low-frequency deep brain stimulation (LFS) at 20 minutes, 6, 24, and 30 hours after the last PTZ injection. Each train of LFS contained 200 pulses at 1 Hz, 200 μA, and 0.1 ms pulse width. One week after the last PTZ injection, the Y-maze test was run, and then the rats' brains were removed, and hippocampal samples were extracted for molecular assessments. The gene expression of two pro-inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)], and glial fibrillary acidic protein (GFAP) immunoreactivity (as a biological marker of astrocytes reactivation) were evaluated.

RESULTS

Obtained results showed a significant increase in the expression of of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and GFAP at one-week post kindling seizures. The application of LFS had a long-lasting effect and restored all of the measured changes toward normal values. These effects were gone along with the LFS improving the effect on working memory in kindled animals.

CONCLUSION

The anti-inflammatory action of LFS may have a role in its long-lasting improving effects on seizure-induced cognitive disorders.

摘要

目的

癫痫伴有炎症,抗炎药物可能具有抗癫痫作用。在本研究中,研究了作为癫痫患者潜在治疗方法的深部脑刺激对癫痫诱发的炎症因子的影响。

材料与方法

在本实验研究中,通过慢性给予戊四氮(PTZ;34mg/Kg)使大鼠点燃癫痫。将动物分为完整组、假手术组、低频深部脑刺激(LFS)组、点燃组和点燃+LFS组。在点燃+LFS组和LFS组中,动物在最后一次PTZ注射后20分钟、6小时、24小时和30小时接受四组海马低频深部脑刺激(LFS)。每组LFS包含200个频率为1Hz、电流为200μA、脉冲宽度为0.1ms的脉冲。在最后一次PTZ注射一周后,进行Y迷宫试验,然后取出大鼠大脑,提取海马样本进行分子评估。评估两种促炎因子[白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)]的基因表达以及胶质纤维酸性蛋白(GFAP)免疫反应性(作为星形胶质细胞重新激活的生物学标志物)。

结果

获得的结果显示,点燃癫痫发作一周后白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)-α和GFAP的表达显著增加。LFS的应用具有持久的效果,并使所有测量的变化恢复到正常值。这些效果伴随着LFS改善了对点燃动物工作记忆的影响。

结论

LFS的抗炎作用可能在其对癫痫诱发的认知障碍的持久改善作用中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af7/7944118/0ce8a109562c/Cell-J-23-85-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af7/7944118/0f5476f73bf2/Cell-J-23-85-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af7/7944118/88247bb2892c/Cell-J-23-85-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af7/7944118/0ce8a109562c/Cell-J-23-85-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af7/7944118/0f5476f73bf2/Cell-J-23-85-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af7/7944118/88247bb2892c/Cell-J-23-85-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1af7/7944118/0ce8a109562c/Cell-J-23-85-g03.jpg

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