Abstracts

Rationale: Epilepsy is a common chronic brain disorder. About 30% of patients with epilepsy do not respond to drug treatment and eventually develop refractory epilepsy. Deep brain stimulation (DBS) is a new neuromodulation method for controlling intractable epilepsy; however, the mechanism of  how DBS controls epilepsy, the optimal stimulus target, and the optimal stimulation parameters are still unclear. In this study, we used a self-developed micro-neurostimulation system programmed to be controlled by a smart phone to deliver continuous low-frequency (1Hz) electrical stimulation to bilateral endopiriform nuclei (EPN). The purpose is to explore new stimulatory targets and stimuli parameters that can control chronic focal epilepsy in rats. Methods: Adult male Sprague-Dawley rats weightng 250-350g were used in this study. Using stereotactic surgery, a segment of cobalt wire (1.0 mm in diameter and 1.5 mm in length) was implanted into the left motor cortex to induce chronic focal epilepsy. Two screw electrodes and two tungsten depth electrodes (D = 177 µm) were symmetrically implanted into the bilateral motor cortex and hippocampal CA1 for EEG recording. Then two bipolar tungsten stimulation electrodes were stereotactically implanted into bilateral EPN. We stimulated each side of the EPN separately and recorded the evoked potential from the ipsilateral hippocampal CA1 region to confirm whether the stimulating electrodes were accurately implanted in the EPN. Final stimulus parameters were adjusted to the intensity required to produce half-maximal evoked potential of each side for each rat. Three days after surgery, all rats were started on long term video-EEG monitoring. At the same time, bilateral EPN were stimulated with low frequency (1Hz) sustained stimulus, and stimulation was stopped after three consecutive days without seizures. All rats were sacrificed after the experiment and the brains were removed for histology to confirm the correct location of the stimulating electrode and to evaluate the safety of the stimulation. Results: Results show that the average number of seizures per day in the EPN stimulation group was significantly reduced (3.2±0.2/d, n=5) compared to the control group (8.1±1.0/d, n=5, P<0.001) and sham stimulation group (7.6±0.8/d, n=5, P<0.001). In addition, the seizure behavioral score (Racine scale) in the EPN stimulation group was lower (3.0±0.2/d, n=5) than the control group (4.1±0.1/d, n=5, P<0.001) and sham stimulation group (4.0±0.2/d, n=5, P<0.001). However, there was no statistically significant difference between the EPN stimulation group and the other two groups in terms of the latency of seizure induction (EPN group 6.6±0.5d, n=5, control group 6.4±0.4d, n=5 and sham stimulation group 5.4±0.2d, n=5, P>