| At present, the treatment of epilepsy mainly includes drugs and operation.Surgical resection of epileptic foci and transection of discharge propagationpathways can reduce seizure frequency in drug-resistant epileptic patients.However, when the epileptogenic foci are embedded within the eloquent cortexor there are several foci verified by EEG, the risks associated with epilepsysurgery may be unacceptable. The strong need to find alternative treatments forepilepsy has led to a resurgence of interest in deep brain stimulation (DBS), atreatment modality that has been used successfully in patients with movementdisorders. Several targets, including the anterior nucleus of the thalamus (ANT),hippocampus, subthalamic nucleus (STN), and substantia nigra pars reticulata(SNr), have all been shown to suppress seizures in animal models. Further,clinical studies often target the centromedian thalamic nucleus, caudate nucleus,hippocampus, ANT, and STN. However, few studies have examined the optimalsites and stimulus parameters for DBS. SNr plays a critical role in the modulation of seizures. It represents the key element of an endogenous anticonvulsant system.Electrical stimulation of SNr suppresses seizures in different animal models.However, most epileptic foci in these models are not located in the neocortex.The anticonvulsant efficacy of high-and low-frequency DBS at theipsilateral, contralateral, and bilateral sites within SNr on ferric chloride-inducedneocortical seizures was investigated in the present study. Results: Injection ofFeCl3into the somatosensory cortex induced multiple EEG-defined seizures overthe6h recording period (average number of seizures:29.42±8.86). Insertion ofthe stimulating electrodes into SNr without DBS had no effect on the number ofseizures in the6h EEG recording relative to the control rats (ipsilateralsham-operated control:31.5±9.81; contralateral sham-operated control:33±7.57; bilateral sham-operated control:28.83±10.12). In contrast, high-frequencystimulation (HFS,130Hz) to the ipsilateral, contralateral, or bilateral SNrsignificantly decreased the number of seizures during the6h EEG recordingperiod (ipsilateral HFS rats:10.17±3.21, P <0.05; contralateral HFS rats:6.33±3.17, P <0.05;bilateral HFS rats:8.83±2.95, P <0.05). However, no significantdifference in the number of seizures was found when low-frequency stimulation(LFS,20Hz) was applied to the ipsilateral, contralateral, or bilateral SNr in the6h EEG recording (ipsilateral LFS rats:26.67±9.0; contralateral LFS rats:27.92±8.66; bilateral LFS rats:28.33±5.55).The duration of seizures in each group was also measured. Comparedwith the control group (average duration of32.07±10.69s), the rats in thesham-operated control subgroups showed no significant reduction in averageseizure duration (ipsilateral sham-operated control:29.52±8.97s; contralateralsham-operated control:32.85±8.19s; bilateral sham-operated control:31.63±9.31s). In the HFS subgroups, the duration of seizures was not reduced significantly following bilateral and unilateral stimulations (bilateral HFS rats:22.20±6.94s, P>0.05; ipsilateral HFS rats:33.87±7.43s, P>0.05;contralateral HFS rats:30.48±5.58s, P>0.05). Similarly, LFS did not alterseizure duration (ipsilateral LFS rats:26.91±11.57s; contralateral LFS rats:28.63±7.88s; bilateral LFS rats:26.9±7.91s).The stimulating sides and frequency have no interaction in reducingnumber of seizures or seizures duration (P>0.05).Conclusions: The HFS of SNr has been demonstrated to reduce the numberof FeCl3-induced focal seizures but not seizures duration in adult rat neocortex.Therefore, the HFS of SNr was effective in reducing ictogenesis, but it failed toreduce the severity of individual seizures. Ipsilateral, contralateral, and bilateralstimulation were all equally effective in suppressing seizures. It suggests thatunilateral HFS needs to be considered first so as to reduce the risks of operationwhen electrical stimulation of SNr is applied against epilepsy in clinic.Furthermore, the stimulating electrode should be placed in non-dominanthemisphere as far as possible. In contrast, LFS (20Hz) had no significant effecton neocortical seizures regardless of whether the stimulation was ipsilateral,contralateral, or bilateral. The frequency of stimulation is paramount insuppressing neocortical seizures in which DBS at least targets SNr. Thestimulating sides and frequency have no interaction. |
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