Effects of the ketogenic diet on neurogenesis after kainic acid-induced seizures in mice

Epilepsy Res. 2008 Feb;78(2-3):186-94. doi: 10.1016/j.eplepsyres.2007.11.010. Epub 2008 Jan 16.


The ketogenic diet (KD) remains a therapy in search of explanation although it is an established treatment of intractable epilepsy. Recent studies suggest that the KD may be both anticonvulsant and antiepileptogenic. Epileptic seizures have been shown to stimulate the proliferation rate of neuronal progenitor cells in adult animals, which may be related to epileptogenesis. It is known that calorie restriction (CR) increases neurogenesis. The KD was originally formulated to reproduce the biochemical changes seen upon fasting (extreme CR). Thus, we investigated the effects of the KD on neurogenesis after kainic acid (KA)-induced seizures in mice. In the present study, quantitative analysis of BrdU labeling revealed a significant increase in the proliferation rate of neuronal progenitor cells after KA-induced seizures in the KD-fed mice. This finding may provide a clue to explain how the KD exerts antiepileptogenic effects although further studies are mandatory to elucidate the relationship between seizure-induced neurogenesis augmented by the KD and its antiepileptogenic properties. In conclusion, our results suggest that the KD enhances neurogenesis, which may be related to its beneficial effects on epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Animals
  • Antimetabolites
  • Bromodeoxyuridine
  • Cell Proliferation / drug effects
  • Convulsants*
  • DNA-Binding Proteins
  • Dentate Gyrus / cytology
  • Dentate Gyrus / pathology
  • Excitatory Amino Acid Agonists*
  • Fluorescent Antibody Technique, Indirect
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / cytology
  • Hippocampus / pathology
  • Immunohistochemistry
  • Kainic Acid*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Nuclear Proteins / metabolism
  • Seizures / chemically induced
  • Seizures / diet therapy*
  • Seizures / pathology*
  • Tissue Fixation


  • Antimetabolites
  • Convulsants
  • DNA-Binding Proteins
  • Excitatory Amino Acid Agonists
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • NeuN protein, mouse
  • Nuclear Proteins
  • Bromodeoxyuridine
  • Kainic Acid
  • 3-Hydroxybutyric Acid