title: Erythropoietin markedly attenuates brain infarct size and improves neurological function in the rat.
abstract: BACKGROUND
  The impact of epoetin beta (recombinant human erythropoietin) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) induced by distal left internal carotid artery occlusion was investigated.
  
  
  METHODS
  Adult male Sprague-Dawley rats (n = 30) were categorized into group 2 (IS only) and group 3 (IS plus intraperitoneal erythropoietin 5000 IU/kg at 0, 12, and 24 hours after IS). Healthy Sprague-Dawley rats (n = 10) served as group 1.
  
  
  RESULTS
  Analysis of brain tissues showed larger BIA in group 2 than in group 3 (P < 0.001). Corner test identified highest frequency of left turn in group 2 (P < 0.05). The mRNA expressions of Bax, caspase 3, interleukin 18, toll-like receptor 4, and plasminogen activator inhibitor 1 were highest, whereas Bcl-2 was lowest in group 2 (P < 0.05). Lower CXCR4 and stromal cell-derived factor 1 expressions were noted in group 2 than in group 3 (P < 0.01). Immunohistofluorescence staining showed lower expressions of CXCR4, stromal cell-derived factor 1, von Willebrand factor, and doublecortin with higher number of apoptotic nuclei in group 2 than in group 3 (P < 0.001). Immunohistochemical staining demonstrated lower cellular proliferation and number of small vessels with higher glial fibrillary acid protein expression in group 2 than in group 3 (P < 0.01).
  
  
  CONCLUSIONS
  Erythropoietin significantly limited BIA and improved sensorimotor dysfunction after acute IS.
authors.affiliation: Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan.
authors.forename: Chun-Man
authors.initials: CM
authors.lastname: Yuen
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Chung
authors.forename: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Sheung-Fat
authors.initials: SF
authors.lastname: Ko
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020520:Brain Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004660:Encephalitis / Q000188:drug therapy / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D006397:Hematinics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000187:drug effects*
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D006397:Hematinics; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin