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J Infect Dis ; 193(7): 987-95, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16518761

RESUMO

Cerebral involvement during malaria is a complication that leads to seizure, coma, and death. The effect of new neuroprotective therapies has not yet been investigated, although cerebral malaria shares some features with neurological stroke. Erythropoietin (EPO) is one of the more promising drugs in this area. We measured the effect of EPO on the survival of mice infected with Plasmodium berghei ANKA and demonstrated that inoculations of recombinant human EPO at the beginning of the clinical manifestations of cerebral malaria protect >90% of mice from death. This drug has no effect on the course of parasitemia. The effect of EPO was not related to either the inhibition of apoptosis in the brain or the regulation of the increase and decrease of nitric oxide production in the brain and blood, respectively. Tumor necrosis factor-alpha and interferon-gamma mRNA overexpression was inhibited by EPO, and treated mice had fewer brain hemorrhages. EPO has been used in patients with chronic diseases for years, and more recently it has been used to treat acute ischemic stroke. The data presented here provide the first evidence indicating that this cytokine could be useful for the symptomatic prevention of mortality during the acute stage of cerebral malaria.


Assuntos
Eritropoetina/uso terapêutico , Malária Cerebral/tratamento farmacológico , Malária/complicações , Fármacos Neuroprotetores/uso terapêutico , Plasmodium berghei , Animais , Apoptose , Encéfalo/patologia , Modelos Animais de Doenças , Eritropoetina/administração & dosagem , Eritropoetina/farmacologia , Feminino , Expressão Gênica , Interferon gama/biossíntese , Interferon gama/genética , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/análise , Parasitemia , RNA Mensageiro/análise , Proteínas Recombinantes , Análise de Sobrevida , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética
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