Age-dependent differences in flurothyl seizure sensitivity in mice treatedwith a ketogenic diet

Despite strong clinical data confirming the anticonvulsant efficacy of a ke togenic diet (KGD) in pediatric patients, corroborative experimental data i n young animals are limited. In the present study, the effects of a KGD on flurothyl seizure susceptibility were examined in normal juvenile mice afte r a dietary duration of 3, 7, or 12 days, and in adult mice for 15 days. In all groups of KGD-treated mice, blood beta-hydroxybutyrate levels were sig nificantly elevated over those measured in controls. The present KGD was an ticonvulsant (i.e. delayed onset) against the first (clonic) flurothyl-indu ced seizure for juvenile mice treated for either 7 or 12 days, but not for juvenile mice and adult mice fed the diet for 3 and 15 days, respectively. While this KGD was not anticonvulsant against the second (tonic extension) seizure induced by flurothyl in any of the juvenile groups, it significantl y delayed tonic extension in the adult group. In addition, juvenile mice fe d a KGD exhibited a lower mortality rate following flurothyl-induced seizur es compared to mice fed a standard diet. In our discussion of animal models of the KGD, we highlight the need to understand better the impact of impor tant variables such as dietary composition, genetic background, and mode of seizure induction in the study of the KGD. (C) 1999 Elsevier Science B.V. All rights reserved.