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

(Pages: 85-92)
Razieh Rohani, M.Sc, 1Abbas Aliaghaei, Ph.D, 1Mohammad-Amin Abdollahifar, Ph.D, 1Yousef Sadeghi, Ph.D, 1Leila Zare, Ph.D., 2Samaneh Dehghan, Ph.D., 2Mohammad Hassan Heidari, Ph.D., 1,*
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
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
*Corresponding Address: P.O.Box: 985717443 Department of Biology and Anatomical Sciences School of Medicine Shahid Beheshti University of Medical Sciences and Health Services (SBMU) Tehran Iran Email:hdr@sbmu.ac.ir
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Rohani Razieh, Aliaghaei Abbas, Abdollahifar Mohammad-Amin, Sadeghi Yousef, Zare Leila, Dehghan Samaneh, Heidari Mohammad Hassan. Long-Term Effects of Hippocampal Low-Frequency Stimulation on Pro-Inflammatory Factors and Astrocytes Activity in Kindled Rats. Cell J. 2021; 23(1): 85-92.

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.