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A dietary therapy for pediatric epilepsy known as the ketogenic diet has seen a revival in its clinical use during the past decade. Although the underlying mechanism of the diet remains unknown, modern scientific approaches, such as the genetic disruption of glucose metabolism, are allowing for more detailed questions to be addressed. Recent work indicates that several mechanisms may exist for the ketogenic diet, including disruption of glutamatergic synaptic transmission, inhibition of glycolysis, and activation of ATP-sensitive potassium channels. Here, we describe on-going work in these areas that is providing a better understanding of metabolic influences on brain excitability and epilepsy.
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