Effects Of Deep Brain Stimulation At The Medial Septum On Temporal Lobe Epilepsy In Mice

Epilepsy is a common chronic brain disease in clinic, characterized by abnormal high synchronization discharge of neurons that can lead to central nervous system dysfunction. Temporal lobe epilepsy (TLE), of which the seizure focus usually originated from hippocampus, is the most common type of refractory epilepsy. Deep brain stimulation (DBS) has become a new strategy for adjuvant epilepsy therapy, but the optimal stimulation target and parameters are still unknown. In this study, in order to explore the effect of DBS at the medial septum (MS) on hippocampal epilepsy, we delivered DBS with different frequencies (1 Hz,5 Hz,20 Hz and 100 Hz) by continuous or intermittent way to MS in kainic acid (KA)-and kindling-induced epilepsy model. In acute KA model, continuous DBS at MS by 1 Hz,5 Hz,20 Hz and 100 Hz controlled generalized seizures (GS) but not focal seizures (FS), indicated by reducing GS incidence, mean seizure stage, number of GS and extending GS latency. Among all the stimulation frequencies,5 Hz showed the strongest inhibition of seizure onsets. Compared with continuous way, intermittent DBS of MS had weaker anti-epileptic effect and only 1 Hz and 5 Hz intermittent stimulation of MS inhibited seizures by reducing number of GS. By analysing power spectra of hippocampal EEG, we found that the anti-epileptic effect of 5 Hz stimulation was related with the reduction of delta rhythm in hippocampus. In addition, in kindling-induced epilepsy model, DBS at MS controlled GS but not kindling acquisition. In conclusion, these results indicated that continuous 5 Hz DBS of MS is effective to inhibit TLE, which may be associated with reduction of delta rhythm in hippocampal EEG and its anti-epileptic effect is frequency-and model-dependent. This result suggests that MS may be a potential target for TLE therapy (DBS or medication treatment) in clinic.