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Abstract
Electroencephalographic (EEG) seizures and behavioral convulsions begin to appear
spontaneously a few weeks after chemoconvulsant-induced status epilepticus (SE) and
thereafter become more intense. This indicates the progressive development of a long-lasting
epileptic focus. In addition, chemoconvulsant-induced SE increases neuronal proliferation
in the dentate subgranular zone (SGZ) and ectopic migration of newborn neurons into
the dentate hilus of adult animals. These seizure-induced newborn neurons, especially
ectopic granule cells in the dentate hilus, are believed to facilitate the development
of epileptic foci in animal models of temporal lobe epilepsy. In the present study,
we examined the effects of a novel antiepileptic drug, levetiracetam, on the appearance
of spontaneous EEG seizures and on the generation of newborn neurons, especially of
ectopic granule cells in the dentate hilus, following kainate-induced SE. Levetiracetam
treatment for 25 days, initiated 24 hours after induction of kainate-induced SE, significantly
decreased the mean duration of spontaneous EEG seizures 58 days later. Levetiracetam
treatment also prevented an SE-induced increase in the number of ectopic granule cells
observed 58 days after kainate administration by suppressing neuronal proliferation
in the dentate SGZ and abnormal migration of newborn neurons from the dentate SGZ
to the hilus. These results are in accord with a previous report that an antimitotic
agent that reduced the number of newborn neurons significantly decreased the frequency
of spontaneous convulsions 1 month after pilocarpine-induced SE. This evidence from
the kainate model of temporal lobe epilepsy suggests that levetiracetam may exert
antiepileptogenic effects through the suppression of seizure-induced neurogenesis.