The protective effect of a ketogenic diet on kainic acid-induced hippocampal cell death in the male ICR mice

This study was designed to evaluate the antiapoptotic effects of a ketogenic diet (KD) through histological (cresyl violet staining, TUNEL staining and immunohistochemistry) and behavioral studies using kainic acid (KA, 25 mg/kg i.p.)-induced seizures in male ICR mice. KA-induced seizure in rodents is widely used as an experimental model for human temporal lobe epilepsy because of their behavioral and pathological similarities. A KA-induced seizure causes neuronal damage in hippocampal pyramidal neurons and involves a caspase-3-mediated apoptotic pathway. In this study, the seizure onset time of the KD-fed group was delayed compared to that of the group fed a normal diet (ND) after a systemic KA injection. Histological studies revealed that KA caused pyknosis in most of the hippocampal areas in the ND-fed group, however, well-preserved pyramidal neurons were detected in the hippocampus of mice that had been on KD for I month, which began on postnatal day 21. The number of TUNEL-positive cells and caspase-3-positive cells in the hippocampus of the KD-fed group was lower than that of the ND-fed group. These findings indicate that KD has an antiepileptic effect via a neuroprotective action that involves the inhibition of caspase-3-mediated apoptosis of hippocampal neurons. (C) 2002 Elsevier Science B.V. All rights reserved.