The Effect Of Low Frequency Stimulation At The Subiculum On Secondary Epileptogenesis In Temporal Lobe Epilepsy

Epilepsy is a common neurological disorder with a global incidence of approximately 1%.It is characterized by recurrent seizures attributed to abnormal synchronization of neuronal discharges at the epileptic focus.After experiencing recurrent seizures,some patients would develop new independent seizure foci outside the primary focus(commonly in the homotopic area of the contralateral hemisphere and sometimes ipsilateral hemispheres),known as “secondary epileptogenesis”.The presence of the secondary focus could cause further pharmacoresistance and relapse after surgery,which brings great danger to the patients.Therefore,it is crucial to find effective preventive treatments for secondary epileptogenesis.Recently,low frequency stimulation has emerged as an alternative treatment for epilepsy due to its potential antiepileptic effect and safety.Our previous studies have already confirmed that low frequency stimulation at the subiculum could effectively retard epileptogenesis and reverse pharmacoresistance of temporal lobe epilepsy at the primary focus,suggesting that it may also be effective for secondary epileptogenesis.Therefore,here we performed kindling stimulations at the right CA3 of mice(primary focus),followed by kindling stimulations at the contralateral hippocampus or ipsilateral entorhinal cortex when the primary focus is kindled to establish an animal model of secondary epileptogenesis in temporal lobe epilepsy.After that,we investigated the effect of low frequency stimulation at the subiculum ipsilateral to the primary focus on secondary epileptogenesis.We found that 1 Hz low frequency stimulation at the subiculum ipsilateral to the primary focus effectively retarded secondary epileptogenesis,characterized by alleviating the initial seizure severity and retarding the kindling acquisition process of the secondary focus.Further preliminary electrophysiology experiments suggested that low frequency stimulation at the subiculum reversed the enhancement of synaptic plasticity between the primary and secondary focus that accompanies the primary epileptogenesis and effectively inhibited the neuronal excitability of the secondary focus.These results suggest that low frequency stimulation at the subiculum could prevent secondary epileptogenesis in temporal lobe epilepsy,and this effect may be attributed to suppressing the enhanced synaptic plasticity between the primary and secondary focus,thereby reducing the neuronal excitability of the secondary focus.