title: Effect of topiramate following recurrent and prolonged seizures during early development.
abstract: Topiramate, an antiepileptic drug with a number of mechanisms of action including inhibition of glutamate activity at the AMPA and KA receptors, was assessed as a neuroprotective agent following seizures. We administered topiramate, 80 mg/kg, or saline for 4 weeks following a series of 25 neonatal seizures or status epilepticus (SE) induced by lithium-pilocarpine in postnatal day 20 rats. Age-matched control rats without a history of seizures were administered topiramate or saline. Following completion of the topiramate injections, animals were tested in the water maze for spatial learning and the brains examined for cell loss and sprouting of mossy fibers. While there was a trend for improved visual-spatial performance in the water maze following topiramate therapy in rats with neonatal seizures, no differences were found in the histological examination of the hippocampus. Neonatal rats exposed to 4 weeks of topiramate did not differ from non-treated controls in water maze performance or histological examination. In weanling rats subjected to SE, topiramate provided a moderate degree of neuroprotection, with topiramate-treated rats performing better in the water maze than rats receiving saline. However, no differences in cell loss or mossy fiber sprouting were found in the histological examination of the brains. These findings demonstrate that chronic treatment with topiramate following SE improves cognitive function. In addition, long-term administration of high-dose topiramate in the normal developing rat brain does not appear to impair cognitive performance.
authors.affiliation: Clinical Neurophysiology Laboratory, Department of Neurology, Center for Research in Pediatric Epilepsy, Harvard Medical School, Children's Hospital Boston, Hunnewell 2, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Cha
authors.forename: Diosely C
authors.initials: DC
authors.lastname: Silveira
authors.forename: Xianzeng
authors.initials: X
authors.lastname: Liu
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Hu
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Holmes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003292:Convulsants; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D005481:Flurothyl; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008094:Lithium / Q000494:pharmacology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000473:pathology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012008:Recurrence; D012107:Research Design; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D018721:Muscarinic Agonists; D010862:Pilocarpine; D000077236:Topiramate; D005632:Fructose; D008094:Lithium; D005481:Flurothyl