title: Erythropoietin: emerging role of erythropoietin in neonatal neuroprotection.
abstract: BACKGROUND
  In the last two decades, there has been considerable evolution in understanding the role of erythropoietin in neuroprotection. Erythropoietin has both paracrine and autocrine functions in the brain. Erythropoietin binding results in neurogenesis, oligodendrogenesis, and angiogenesis. Erythropoietin and its receptor are upregulated by exposure to hypoxia and proinflammatory cytokines after brain injury. While erythropoietin aids in recovery of locally injured neuronal cells, it provides negative feedback to glial cells in the penumbra, thereby limiting extension of injury. This forms the rationale for use of recombinant erythropoietin and erythropoietin mimetics in neonatal and adult injury models of stroke, traumatic brain injury, spinal cord injury, intracerebral hemorrhage, and neonatal hypoxic ischemia.
  
  
  METHODS
  Review of published literature (Pubmed, Medline, and Google scholar).
  
  
  RESULTS
  Preclinical neuroprotective data are reviewed, and the rationale for proceeding to clinical trials is discussed. Results from phase I/II trials are presented, as are updates on ongoing and upcoming clinical trials of erythropoietin neuroprotection in neonatal populations.
  
  
  CONCLUSIONS
  The scientific rationale and preclinical data for erythropoietin neuroprotection are promising. Phase II and III clinical trials are currently in process to determine the safety and efficacy of neuroprotective dosing of erythropoietin for extreme prematurity and hypoxic-ischemic encephalopathy in neonates.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, Washington.
authors.forename: Vijayeta
authors.initials: V
authors.lastname: Rangarajan
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, Washington. Electronic address: sjuul@uw.edu.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Juul
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy*; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin
keywords: brain; cytokine; erythropoietin; hypoxic-ischemic encephalopathy; neuroprotection; prematurity