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Neurochem Int ; 58(3): 385-90, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21185899

RESUMO

Recent research data have shown that systemic administration of pyruvate and oxaloacetate causes an increased brain-to-blood glutamate efflux. Since increased release of glutamate during epileptic seizures can lead to excitotoxicity and neuronal cell death, we tested the hypothesis that glutamate scavenging mediated by pyruvate and oxaloacetate systemic administration could have a neuroprotective effect in rats subjected to status epilepticus (SE). SE was induced by a single dose of pilocarpine (350mg/kgi.p.). Thirty minutes after SE onset, a single dose of pyruvate (250mg/kgi.p.), oxaloacetate (1.4mg/kgi.p.), or both substances was administrated. Acute neuronal loss in hippocampal regions CA1 and hilus was quantitatively determined five hours after SE onset, using the optical fractionator method for stereological cell counting. Apoptotic cascade in the hippocampus was also investigated seven days after SE using caspase-1 and -3 activity assays. SE-induced neuronal loss in CA1 was completely prevented in rats treated with pyruvate plus oxaloacetate. The SE-induced caspase-1 activation was significantly reduced when rats were treated with oxaloacetate or pyruvate plus oxaloacetate. The treatment with pyruvate and oxaloacetate caused a neuroprotective effect in rats subjected to pilocarpine-induced SE.


Assuntos
Degeneração Neural/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Ácido Oxaloacético/farmacologia , Ácido Pirúvico/farmacologia , Estado Epiléptico/prevenção & controle , Animais , Modelos Animais de Doenças , Masculino , Degeneração Neural/etiologia , Ácido Oxaloacético/uso terapêutico , Ácido Pirúvico/metabolismo , Ratos , Ratos Wistar , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/complicações
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