Erythropoietin markedly attenuates brain infarct size and improves neurological function in the rat

J Investig Med. 2010 Oct;58(7):893-904. doi: 10.231/JIM.0b013e3181e80c40.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / drug effects
  • Brain Infarction / drug therapy*
  • Brain Infarction / metabolism
  • Brain Infarction / pathology*
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Disease Models, Animal
  • Doublecortin Protein
  • Encephalitis / drug therapy
  • Encephalitis / pathology
  • Erythropoietin / pharmacology*
  • Hematinics / pharmacology*
  • Humans
  • Male
  • Neovascularization, Physiologic / drug effects
  • Neurogenesis / drug effects
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Recovery of Function / drug effects*

Substances

  • Dcx protein, rat
  • Doublecortin Protein
  • Hematinics
  • Recombinant Proteins
  • epoetin beta
  • Erythropoietin