Hippocampal DBS affects disease development in the kainic acid rat model for temporal lobe epilepsy

• ¹ Ghent University, Neurology, Belgium
• ² Amsterdan University, Department of Neurobiology, Netherlands

Rationale: There is increasing evidence that the effect of deep brain stimulation (DBS) on seizures increases with prolonged treatment suggesting a disease modifying potential for DBS. To further investigate this, we studied the effect of hippocampal DBS on seizure development in the kainic acid (KA)-induced status epilepticus (SE) model for temporal lobe epilepsy (TLE). Methods: Rats were implanted with a quadripolar DBS/EEG-recording electrode in the right hippocampus and a bipolar EEG-recording electrode in the left hippocampus. 24 hours after kainic acid (KA) induced status epilepticus (SE), one group (n=10) was subjected to long-term DBS (LT-DBS) (Poisson Distributed Stimulation, 130 PPS, 100µs PW, 100µA) during 23 weeks. A control group (n=8) received sham stimulation (SHAM). Video-EEG was recorded continuously during 30 weeks in both groups. Results: During stimulation, the gradual increase in seizure frequency is lower in the DBS group compared to the SHAM group, resulting in significant lower seizure frequencies from week 22 to 25 after SE (p<0.05). In the LT-DBS group 5/10 (50%) of the treated rats showed no gradual increase in daily seizure frequency seizure frequency during 23 weeks of stimulation and were defined as responders. In the SHAM group all rats experienced a gradual increase in seizure frequency during the first 23 weeks after SE. This results in a significantly lower seizure rate in the responder rats compared to the SHAM rats from week 16 to 24 after SE (p<0.01). When stimulation was stopped after 23 weeks, an increase in daily seizure frequency occurred in all responder rats within one week. This resulted in similar seizure rates from week 25 to week 30 in the responder rats and SHAM group (fig.1). No significant differences in seizure rate were observed between the non-responder group and SHAM group during DBS. For all rats, a sigmoid curve could be fitted to the seizure rate data. Statistical analysis of the fitted sigmoid curve’s equation parameters show that only the time after SE at which the EEG seizure frequency in disease development reached half-maximum was significantly retarded from 13.5 weeks post SE in the SHAM group to 24.7 weeks post SE in the responder group (p<0.01)(fig.2A&B). Conclusion: Starting treatment with hippocampal DBS 24h after SE in the post-SE KA model retards normal disease progression in 5/10 (50%) of all treated rats by efficiently suppressing seizures. We show that DBS started 24 hours after the start of SE suppresses the gradual increase in daily seizure frequency that is typically observed in the post-SE KA model.