Calorie Restriction and Ketogenic Diet Diminish Neuronal Excitability in Rat Dentate Gyrus In Vivo

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Abstract
Summary: Purpose: The ketogenic diet (KD) is an effective treatment for intractable epilepsy. However, little is known about its underlying mechanisms. Methods: In this study, in vivo extracellular field responses to angular bundle stimulation were recorded in the dentate gyrus of Sprague–Dawley rats fed one of three diets: ketogenic calorie‐restricted (KCR), normal calorie‐restricted (NCR), or normal ad libitum (NAL). Input/output curves and paired‐pulse relations were used to assess network excitability. A maximal dentate activation (MDA) protocol was used to measure electrographic seizure threshold and duration. Results: Animals fed calorie‐restricted (CR) diets exhibited greater paired‐pulse inhibition, an elevated MDA threshold, and an absence of spreading depression‐like events compared with ad libitum‐fed controls. In the MDA model of epileptogenesis, the rate of increase in electrographic seizure duration after repeated stimuli was markedly reduced in KCR‐fed animals compared with NCR‐ and NAL‐fed controls. Conclusions: These data suggest that CR, by itself, can be anticonvulsant, and treatment with a KCR diet may be both anticonvulsant and antiepileptogenic.