Intermittent fasting reduces interictal epileptiform discharges and hippocampal reactive astrogliosis during electrical kindling epileptogenesis

It has been proposed that interictal epileptiform discharges observed in epilepsy-related structures, such as the hippocampus contributes to epileptogenesis. Intermittent fasting (IF) produces anticonvulsant effects protecting against experimentally induced seizures. It has been suggested that protective effects could be associated with astrocytic metabolic changes. However, it is unknown whether IF modifies the epileptogenic process. Therefore, this work aimed to analyze the impact of IF on interictal epileptiform discharges in the rat hippocampus and their possible correlation with astrocytic activation. Male Wistar rats were divided into two groups: one group had free access to food, while the other group was subjected to IF (food was provided for 2 h a day). Both groups underwent a hippocampal electrical kindling protocol with 36 stimulations. Our results showed that IF inhibited the incidence of generalized seizures induced by kindling and significantly reduced the total spectral power of interictal epileptiform discharges in the hippocampus. Furthermore, IF prevented the rise in fasting blood glucose and reduced seizure-induced astrogliosis by preventing the GFAP expression and the morphological complexity of astrocytes in the hippocampal CA3 region. These results support the notion that IF modifies epileptogenesis by modulating hippocampal hyperexcitability during the interictal stage, which could be associated with reductions in glucose metabolism and astrogliosis.