title: Recombinant human erythropoietin prevents the death of mice during cerebral malaria.
abstract: 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.
authors.affiliation: Equipe d'Accueil 37-32, Parasitologie et Médicine Tropicale, Faculté de Médecine, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Kaiser
authors.forename: Anthony
authors.initials: A
authors.lastname: Texier
authors.forename: Josette
authors.initials: J
authors.lastname: Ferrandiz
authors.forename: Alain
authors.initials: A
authors.lastname: Buguet
authors.forename: Anne
authors.initials: A
authors.lastname: Meiller
authors.forename: Christine
authors.initials: C
authors.lastname: Latour
authors.forename: François
authors.initials: F
authors.lastname: Peyron
authors.forename: Raymond
authors.initials: R
authors.lastname: Cespuglio
authors.forename: Stéphane
authors.initials: S
authors.lastname: Picot
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008288:Malaria / Q000150:complications*; D016779:Malaria, Cerebral / Q000188:drug therapy*; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000032:analysis; D018512:Parasitemia; D010962:Plasmodium berghei; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D009569:Nitric Oxide; D007371:Interferon-gamma