RESUMO
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.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Frutose/análogos & derivados , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Fármacos Neuroprotetores/uso terapêutico , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Feminino , Frutose/uso terapêutico , Hipóxia/complicações , Hipóxia/tratamento farmacológico , Hipóxia/patologia , Estudos Longitudinais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Ratos , Ratos Sprague-Dawley , TopiramatoRESUMO
Ten-day-old rat pups (P10) subjected to acute hypoxia (down to 4% O2) had as adults increased aggression (handling test), memory impairment (water maze test), and decreased CA1 cell counts. Pups subjected to chronic hypoxia (10% O2 from P0 to P21) had increased aggression, hyperactivity (open-field test), and decreased CA1 cell counts. Chronic hypoxia with superimposed acute hypoxia resulted in consequences that were not different from those of chronic hypoxia.