Hippocampal High-Frequency Stimulation Inhibites the Progression of Rapid Kindling-Induced Seizure in Rats

Epilepsy is a central nervous system disorder (neurological disorder) in which nerve cell activity in the brain becomes disrupted, causing seizures or periods of unusual behavior, sensations and sometimes loss of consciousness. Seizure symptoms can vary widely. It can be treated by drugs or surgeries. However, pharmaco-resistant epilepsy patients are poorly controlled or their seizures are refractory to drug treatment, then resective surgery is frequently a promising therapy in this population; while not all the patients meet the eligibility criteria for the surgical treatment.

In recent years, deep brain stimulation has been investigated in clinical studies and animal studies as an alternative treatment, but the optimal stimulation parameters remain an issue. The present study was designed to investigate the effect of unilateral high-frequency stimulation (HFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats, and compared the results with those of low-frequency stimulation previously published by the authors’ group.

In this study, the authors used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK; n = 7) received only RK stimulus, while the treated group (HFS-hRK; n = 9) received also HFS (biphasic square wave pulses, 130 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing 78% (p < 0.01) of the animals receiving HFS treatment were still not fully kindled staying in stages 0 - III (p < 0.01). HFS group needed a higher number of stimulations to achieve stage III (p <0.05) with respect to control group. However, no significant differences in the cumulative daily afterdischarge duration were observed. HFS did not present significant differences compared with LFS in any of studied parameters.

In conclusion, the findings suggest that unilateral HFS applied on hippocampus effectively inhibited the epileptogenic process induced by hippocampal rapid kindling. According to the comparative results about hippocampal rapid kindled animals stimulated with HFS and LFS (5 Hz), there wasn’t conclusive information on which treatment was most efficient.

Article by Belen Gori, et al, from Argentina.

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