Effect of Unilateral Low-Frequency Stimulation of Hippocampus on Rapid Kindling—Induced Seizure Development in Rats

Abstract

Since the last decade deep brain stimulation has been proposed as an alternative treatment for patients who do not become seizure-free with the current pharmacological treatments and cannot undergo resective surgical procedure. However, the optimal stimulation parameters remain undetermined and active research in humans and animals is necessary. The present study was designed to investigate the effect of unilateral Low Frequency Stimulation (LFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats. We 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 = 6) received only RK stimulus, while the treated group (LFS-hRK; n = 8) received also LFS (biphasic square wave pulses, 1 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing on day 3, 62% (P < 0.05) of the animals receiving LFS treatment were still not fully kindled staying in stages 0-III (P < 0.01). The number of stimulations needed to achieve generalized seizures (stage IV-V of Racine scale) was significantly higher (P < 0.05) in the LFS group with respect to control group. No significant differences in the cumulative daily afterdischarge duration were observed between both groups. These findings suggest that preemptive LFS can significantly decrease the incidence of hippocampus-kindled seizures and delay the progression and secondary generalization of focal seizures

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

“…The HFS group showed a lower incidence of full kin- dling when compared to LFS group, but did not reach significance (Figure 3). We did not observe any differences in relation to the daily achieved seizure stage, between HFS and LFS treatments (LFS data previously published by our group [28]; Figure 1(b) for HFS).…”

“…The surgery was carried out according to Toibaro et al [28]. The rats were deeply anaesthetized with intraperitoneal injections of a ketamine/xylazine mixture at a concentration of 85.0 mg/ml ketamine and 15.0 mg/ml xylazine.…”

“…The HFS (biphasic square wave pulses 50 μA, 130 Hz for 30 seconds) was applied to the treated group immediately before each one of the 12 RK stimulations on three stimulation days. HFS parameters were determined according to Goodman et al 2005 [19] and our preliminary experiments [28].…”

“…Several studies using traditional kindling in different anatomical targets have evaluated the inhibitory effect of low frequency stimulation [19][20][21][22][23] and high-frequency stimulation [24][25][26]. Few reports have been carried out in hippocampus using RK model [25,27,28], moreover for its role in epileptogenesis [29][30][31].…”

“…This study was tested the efficacy of unilateral highfrequency stimulation (HFS) on hippocampus using the RK model and compared with our previous results on low frequency stimulation (LFS) in the same model [28].…”