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

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 mu A, 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-alpha)], 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)-alpha, 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.