Abstract
Deep brain stimulation (DBS) has been investigated for the treatment of epilepsy. In rodents, an increase in the latency for the development of seizures and status epilepticus (SE) has been reported in different animal models but the consequences of delivering stimulation to chronic epileptic animals have not been extensively addressed. We study the effects of anterior thalamic nucleus (AN) stimulation at different current intensities in rats rendered epileptic following pilocarpine (Pilo) administration. Four months after Pilo-induced SE, chronic epileptic rats were bilaterally implanted with AN electrodes or had sham-surgery. Stimulation was delivered for 6 h/day, 5 days/week at 130 Hz, 90 µsec. and either 100 µA or 500 µA. The frequency of spontaneous recurrent seizures in animals receiving stimulation was compared to that recorded in the preoperative period and in rats given sham treatment. To investigate the effects of DBS on hippocampal excitability, brain slices from animals receiving AN DBS or sham surgery were studied with electrophysiology. We found that rats treated with AN DBS at 100 µA had a 52% non-significant reduction in the frequency of seizures as compared to sham-treated controls and 61% less seizures than at baseline. Animals given DBS at 500 µA had 5.1 times more seizures than controls and a 2.8 fold increase in seizure rate as compared to preoperative values. In non-stimulated controls, the average frequency of seizures before and after surgery remained unaltered. In vitro recordings have shown that slices from animals previously given DBS at 100 µA had a longer latency for the development of epileptiform activity, shorter and smaller DC shifts, and a smaller spike amplitude compared to non-stimulated controls. In contrast, a higher spike amplitude was recorded in slices from animals given AN DBS at 500 µA.
Highlights
30% of patients with epilepsy continue to have seizures despite adequate medical treatment [1]
We show that stimulation at parameters that approximate those used in clinical practice [22,23] decreases the frequency of seizures and is associated with a reduction in hippocampal excitability
Effects of anterior thalamic nucleus (AN) Deep brain stimulation (DBS) in vivo Our first experiment consisted in characterizing the effects of AN DBS against spontaneous recurrent seizures in vivo
Summary
30% of patients with epilepsy continue to have seizures despite adequate medical treatment [1]. In this refractory population, surgery often comprises an effective therapeutic modality. Though resective procedures are still considered to be the surgical treatment of choice, some patients are not deemed to be good candidates because of multiple seizure foci, foci in eloquent brain regions or foci that cannot be identified. Under these circumstances, neuromodulation strategies represent a potential alternative [2,3,4]. In the only study addressing the effects of DBS in chronic epileptic animals, AN stimulation had a proconvulsant effect [21]
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