title: Potential neuroprotective effects of continuous topiramate therapy in the developing brain.
abstract: Because antiepileptic drug therapy is usually given chronically with resulting concerns about long-term neurotoxicity, and because short-term topiramate (TPM) therapy has been reported to be neuroprotective against the effects of acute hypoxia, we investigated the long-term effects of continuous TPM therapy during early stages of development. Four groups of rat pups were studied: two sham manipulated normoxia groups and two acute hypoxia groups (at postnatal day [P] 10 down to 4% O(2)), each injected intraperitoneally daily with either vehicle or TPM (30 mg/kg) from P0 to P21. TPM therapy prevented hypoxia-induced long-term (P81) memory impairment (Morris water maze) as well as aggressivity (handling test). The hypoxia group receiving TPM also showed a trend toward reduced CA1 hippocampal cell loss. The aforementioned TPM therapy had no long-term deleterious effects on memory, hyperactivity, or CA1 cell counts in the TPM normoxia group as compared with normal controls.
authors: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. mohamad.mikati@duke.edu
authors: Mohamad A
authors: MA
authors: Mikati
authors: Rita
authors: R
authors: Daderian
authors: Michele
authors: M
authors: Zeinieh
authors: A Soren
authors: AS
authors: Leonard
authors: Diana
authors: D
authors: Azzam
authors: Rana
authors: R
authors: Kurdi
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077236:Topiramate
chemical_list: D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose