title: Levetiracetam suppresses development of spontaneous EEG seizures and aberrant neurogenesis following kainate-induced status epilepticus.
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.
authors.affiliation: Department of Psychiatry, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. ys3524@hotmail.com
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugaya
authors.forename: Eiichi
authors.initials: E
authors.lastname: Maru
authors.forename: Koutaro
authors.initials: K
authors.lastname: Kudo
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Shibasaki
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D018398:Homeodomain Proteins / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000009:adverse effects / Q000494:pharmacology; D000077287:Levetiracetam; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000503:physiopathology / Q000517:prevention & control; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013744:Tetanus Toxin / Q000134:cerebrospinal fluid; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D018697:Nootropic Agents; D013744:Tetanus Toxin; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D000077287:Levetiracetam; D001973:Bromodeoxyuridine; D007608:Kainic Acid; D010889:Piracetam