KETOGENIC DIET | Animal Models of the Ketogenic Diet and Other Dietary Therapies

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The ketogenic diet (KD) is an effective therapy for many children and adults with epilepsy who are refractory to conventional antiepileptic drugs. Possible mechanisms of the KD include direct effects of ketones or lipids on neuronal excitability, enhancement of inhibitory GABAergic function, or alteration of energy metabolism. Another possibility, arising from the fact that carbohydrates are restricted in the KD, is that inhibition of glycolysis (the primary route of glucose catabolism in mammalian cells) might provide an antiepileptic effect. Experiments described in this article show that the glycolysis inhibitor, 2-deoxy-d-glucose, exerts both anticonvulsant and antiepileptic effects in a variety of animal models. Anticonvulsant effects include increase in the afterdischarge threshold in perforant path kindled rats, and decrease in epileptic burst frequency in several models of interictal bursting (including high potassium, 4-aminopyridine, and bicuculline). Antiepileptic effects include the decrease in progression of afterdischarge threshold in kindling of the perforant path, and slowing of kindling progression with perforant path or olfactory bulb stimulation. These findings indicate that 2-deoxy-d-glucose, a safe compound already used for decades in positron emission tomography imaging, might be a novel agent for seizure control in patients with refractory epilepsy.

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