Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

Body weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p < 0.001) reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups.The results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone bodies for energy is predicted to manage EL epileptic seizures through multiple integrated changes of inhibitory and excitatory neural systems.Epilepsy is a neurological disorder involving recurrent abnormal discharges of neurons that produce epileptic seizures [1]. With the exception of stroke, epilepsy is one of the most prevalent human neurological afflictions affecting about 1% of the US population [2,3]. Many persons with epilepsy manifest partial or generalized seizures without symptoms of brain abnormality, i.e., idiopathic epilepsy [1,4,5]. In contrast to idiopathic epilepsy, symptomatic or acquired epilepsy often accompanies brain trauma, injury, or neurostructural defects. While some idiopathic epilepsies are inherited as simple Mendelian traits, most are multifactorial where more than one gene together with environmental factors contribute to the disease phenotype [6,7].Epilepsy animal models are used widely to test the influence of environmental and genetic factors on seizure mechanisms. The epileptic EL mouse is a natural model for human multifactorial idiopathic epilepsy and was first discovered in 1954 in an outbred DDY mouse colony [6,8-10]. EL mice experience complex pa