title: A systematic review and meta-analysis of erythropoietin in experimental stroke.
abstract: Erythropoietin (EPO) has shown promise as a neuroprotectant in animal models of ischemic stroke. EPO is thought not only to protect neurons from cell death, but also to promote regeneration after stroke. Here, we report a systematic review and meta-analysis of the efficacy of EPO in animal models of focal cerebral ischemia. Primary outcomes were infarct size and neurobehavioral outcome. Nineteen studies involving 346 animals for infarct size and 425 animals for neurobehavioral outcome met our inclusion criteria. Erythropoietin improved infarct size by 30.0% (95% CI: 21.3 to 38.8) and neurobehavioral outcome by 39.8% (33.7 to 45.9). Studies that randomized to treatment group or that blinded assessment of outcome showed lower efficacy. Erythropoietin was tested in animals with hypertension in no studies reporting infarct size and in 7.5% of the animals reporting neurobehavioral outcome. These findings show efficacy for EPO in experimental stroke, but when the impact of common sources of bias are considered, this efficacy falls, suggesting we may be overestimating its potential benefit. As common human co-morbidities may reduce therapeutic efficacy, broader testing to delineate the range of circumstances in which EPO works best would be beneficial.
authors.affiliation: Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Jerndal
authors.forename: Kalle
authors.initials: K
authors.lastname: Forsberg
authors.forename: Emily S
authors.initials: ES
authors.lastname: Sena
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Macleod
authors.forename: Victoria E
authors.initials: VE
authors.lastname: O'Collins
authors.forename: Thomas
authors.initials: T
authors.lastname: Linden
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016208:Databases, Factual; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin