title: Neuroprotective effect of levetiracetam on hippocampal sclerosis-like change in spontaneously epileptic rats.
abstract: The spontaneously epileptic rat (SER) begins to exhibit both tonic convulsions and absence seizures from 6 weeks of age and SERs have stable seizures after 10 weeks of age. Low-dose administrations of levetiracetam (LEV) for 4- to 5-weeks-old SERs which did not show spontaneous seizures reduced both seizures 5 weeks after termination of administration. The hippocampus of SER exhibited decreased CA3 neurons, sprouting of mossy fibers, and hyperexpression of the brain-derived neurotrophic factor (BDNF). We attempted prophylactic LEV administrations in preseizure-manifesting SERs to evaluate if such a treatment regimen would protect the hippocampal sclerosis-like changes observed in SERs. The osmotic mini-pump administered LEV dissolved in saline to 4-weeks-old SERs for 4 weeks at 2.5 μl/h. LEV was administered at 420 mg/ml for 4 weeks in Group A. In Group B, LEV was given at 420 mg/ml for the first 2 weeks followed by doubling the dosage (840 mg/ml) in the following 2 weeks. LEV administrations in preseizure-manifesting SERs reduced the decrease of CA3 neurons and mossy fibers sprouting at 10-11 weeks of age in both group A and B. LEV attenuated BDNF expression in inner molecular layers of the dentate gyrus, striatum radiatum, and CA3 in 10- to 11- and 14- to 15-weeks-old SERs. In group B, LEV decreased BDNF expression in hilus and CA1 of 10- to 11- weeks-old SER. The present results suggest that prophylactic treatment with LEV in preseizure-manifesting SERs inhibits hippocampal sclerosis-like neuronal degeneration and/or regeneration.
authors.affiliation: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Sugata
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hanaya
authors.forename: Kenta
authors.initials: K
authors.lastname: Kumafuji
authors.forename: Mai
authors.initials: M
authors.lastname: Tokudome
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.forename: Masashi
authors.initials: M
authors.lastname: Sasa
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D000077287:Levetiracetam; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D010889:Piracetam / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D010919:Placebos; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012598:Sclerosis / Q000473:pathology / Q000517:prevention & control*; D012640:Seizures / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010919:Placebos; D000077287:Levetiracetam; D010889:Piracetam