Ketogenic diet exhibits neuroprotective effects in hippocampus but fails to prevent epileptogenesis in the lithium‐pilocarpine model of mesial temporal lobe epilepsy in adult rats

Abstract

Although the number of antiepileptic drugs (AEDs) is increasing, none displays neuroprotective or antiepileptogenic properties that could prevent status epilepticus (SE)-induced drug-resistant epilepsy. Ketogenic diet (KD) and calorie restriction (CR) are proposed as alternative treatments in epilepsy. Our goal was to assess the neuroprotective or antiepileptogenic effect of these diets in a well-characterized model of mesial temporal lobe epilepsy following initial SE induced by lithium-pilocarpine in adult rats. Seventy-five P50 male Wistar rats were fed a specific diet: normocalorie carbohydrate (NC), hypocalorie carbohydrate (HC), normocalorie ketogenic (NK), or hypocalorie ketogenic (HK). Rats were subjected to lithium-pilocarpine SE, except six NC to constitute a control group for histology (C). Four rats per group were implanted with epidural electrodes to record electroencephalography (EEG) during SE and the next six following days. From the seventh day, the animals were video-recorded 10 h daily to determine latency to epilepsy onset. Neuronal loss in hippocampus and parahippocampal cortices was analyzed 1 month after the first spontaneous seizure. After lithium-pilocarpine injection, neither KD nor CR modified SE features or latency to epilepsy. In hippocampal layers, KD or CR exhibited a neuroprotective potential without cooperative effect. Parahippocampal cortices were not protected by the diets. The antiepileptic effect of KD and/or CR is overwhelmed by lithium-pilocarpine injection. The isolated protection of hippocampal layers induced by KD or CR or their association failed to modify the course of epileptogenesis.