J Korean Child Neurol Soc.  2003 May;11(1):24-36.

Protective Effect of Ketogenic Diet on the Hippocmpal Damage Produced by Pilocarpine-induced Status Epilepticus in Rats

Affiliations
  • 1Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea. ksulee@cnu.ac.kr
  • 2Department of Neurology, College of Medicine, Chungnam National University, Daejeon, Korea.
  • 3Department of Pediatrics, College of Medicine, Inje University, Ilsan Paik Hospital, Goyang, Korea.

Abstract

PURPOSE: Although ketogenic diet(KD) is an old method of treating epilepsies, its outstanding antiepileptic effect in some epileptic patients need re-evaluation. This study was performed to evaluate the anti-epiletogenic effect of KD.
METHODS
In the preliminary experiment, to select a proper animal model of status epilepticus(SE), an evaluation of EEG and behavioral characteristics of pilocarpine-induced SE model was done in 12 Sprague-Dawley rats. As the aim of the first experiment was to evaluate neuronal death in the hippocampus of similarly convulsed rats, the 10-20 mg/kg of diazepam i.p. injection was given to cease SE in each stage of SE in KD and regular diet(RD) rats. Previous diet was maintained for two weeks until the evaluation of pathological changes with H-E and C-V stainings(64 rats, second experiments). In order to investigate whether the differences in the neuronal damage cause different mossy fiber sprouting or not, 40 rats were fed with KD and RD(20 rats each) 4 hours before pilocarpine-induced SE. After the treatment of SE with diazepam, half of previous KD rats maintained with KD and remaining 10 rats were fed with RD. Also previous RD rats were fed with RD and KD in the same way. Mossy fiber sprouting and synaptic reorganization was determined by Timm's staining 4 weeks after SE.
RESULTS
Pilocarpine-induced SE showed reliable EEG and behavioral patterns in all rats. Also, KD did not have any influence on SE induced by pilocarpine in terms of SE induction time and severity. Neuronal damages in CA1, CA3, and dentate gyrus were less prominent in the KD rats in every SE stage. Rats with RD before their SE showed significant Timm's(+) bands, whereas rats with KD after the SE did not show any differences.
CONCLUSION
KD consistently protect neuronal damage caused by seizures in the hippocampus. This neuroprotection causes less mossy fiber synaptic reorganization.

Keyword

Pilocarpine; Status epilepticus; Hippocampus; Ketogenic diet; Timm's staining; Neuronal damage

MeSH Terms

Animals
Dentate Gyrus
Diazepam
Diet
Electroencephalography
Epilepsy
Hippocampus
Humans
Ketogenic Diet*
Models, Animal
Neurons
Pilocarpine
Rats*
Rats, Sprague-Dawley
Seizures
Status Epilepticus*
Diazepam
Pilocarpine
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