The relationship between erythropoietin pretreatment with blood-brain barrier and lipid peroxidation after ischemia/reperfusion in rats

Life Sci. 2007 Mar 13;80(14):1245-51. doi: 10.1016/j.lfs.2006.12.014. Epub 2007 Jan 9.


Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including ischemia and some neurodegenerative disorders. In recent years, erythropoietin (EPO) has been shown to exert neuroprotection in many pathological conditions including ischemia in the brain. This study aimed to investigate the effects of EPO on BBB integrity, infarct size and lipid peroxidation following global brain ischemia/reperfusion in rats. Wistar male rats were divided into four groups (each group n=8); Group I; control group (sham-operated), Group II; ischemia/reperfusion group, Group III; EPO treated group (24 h before decapitation--000 U/kg r-Hu EPO i.p.), Group IV; EPO+ ischemia/reperfusion group (24 h before ischemia/reperfusion--3000 U/kg r-Hu EPO i.p.). Global brain ischemia was produced by the combination of bilateral common carotid arteries occlusion and hemorrhagic hypotension. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage was observed for BBB integrity. Infarct size was calculated based on 2,3,5-triphenyltetrazolium chloride (TTC) staining. Lipid peroxidation in the brain tissue was determined as the concentration of thiobarbituric acid-reactive substances (TBARS) for each group. Ischemic insult caused bilateral and regional BBB breakdown (hippocampus, cortex, corpus striatum, midbrain, brain stem and thalamus). EPO pretreatment reduced BBB disruption, infarct size and lipid peroxide levels in brain tissue with 20 min ischemia and 20 min reperfusion. These results suggest that EPO plays an important role in protecting against brain ischemia/reperfusion through inhibiting lipid peroxidation and decreasing BBB disruption.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain Infarction / drug therapy
  • Brain Infarction / metabolism
  • Brain Infarction / pathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Carotid Arteries / pathology
  • Carotid Arteries / physiopathology
  • Carotid Stenosis / pathology
  • Carotid Stenosis / physiopathology
  • Disease Models, Animal
  • Drug Administration Schedule
  • Epoetin Alfa
  • Erythropoietin / therapeutic use*
  • Evans Blue / metabolism
  • Lipid Peroxidation / drug effects*
  • Male
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Thiobarbituric Acid Reactive Substances / metabolism


  • Neuroprotective Agents
  • Recombinant Proteins
  • Thiobarbituric Acid Reactive Substances
  • Erythropoietin
  • Evans Blue
  • Epoetin Alfa