title: The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models.
abstract: OBJECTIVE
  Erythropoietin (EPO) shows promise as a neuroprotective agent in animal models of traumatic brain injury (TBI). However, clinical trials of the efficacy of EPO treatment in patients with TBI yield conflicting results. The authors conducted a systematic review and meta-analysis to assess the effect of EPO in experimental animal models of TBI, the goal being to inform the design of future clinical trials.
  
  
  METHODS
  The authors identified eligible studies by searching PubMed, Web of Science, MEDLINE, Embase, and Google Scholar in October 2013. Data were pooled using the random-effects model, and results were reported in terms of standardized mean difference. Statistical heterogeneity was examined using both I(2) and chi-square tests, and the presence of small study effects was investigated with funnel plots and Egger tests. In-depth analyses were performed for lesion volume and neurobehavioral outcome, and the studies' methodological quality was also evaluated.
  
  
  RESULTS
  Of a total of 290 studies, 13 found an effect of EPO on lesion volume and neurobehavioral outcome. Overall, the methodological quality of the studies was poor, and there was evidence of statistical heterogeneity among the publications as well as small-study effects. However, in-depth analyses showed statistically significant findings in favor of a beneficial effect of EPO after TBI.
  
  
  CONCLUSIONS
  Despite limitations of this systematic review that may have influenced the findings, the authors conclude that EPO might be beneficial in treating experimental TBI in terms of reducing lesion volume and improving neurobehavioral outcome. However, this review also indicates that more well-designed and well-reported animal studies are needed.
authors.affiliation: Institute of Integrated Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Peng
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Xing
authors.forename: Jingjing
authors.initials: J
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Weihao
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D018849:Controlled Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin
keywords: EPO = erythropoietin; MWM = Morris water maze; SMD = standardized mean difference; STAIR = Stroke Therapy Academic Industry Roundtable; TBI = traumatic brain injury; efficacy; erythropoietin; mNSS = modified Neurological Severity Score; systematic review; traumatic brain injury