A potential role for erythropoietin in focal permanent cerebral ischemia in mice

J Cereb Blood Flow Metab. 1999 Jun;19(6):643-51. doi: 10.1097/00004647-199906000-00007.


The present study describes, for the first time, a temporal and spatial cellular expression of erythropoietin (Epo) and Epo receptor (Epo-R) with the evolution of a cerebral infarct after focal permanent ischemia in mice. In addition to a basal expression of Epo in neurons and astrocytes, a postischemic Epo expression has been localized specifically to endothelial cells (1 day), microglia/macrophage-like cells (3 days), and reactive astrocytes (7 days after occlusion). Under these conditions, the Epo-R expression always precedes that of Epo for each cell type. These results support the hypothesis that there is a continuous formation of Epo, with its corresponding receptor, during the active evolution of a focal cerebral infarct and that the Epo/Epo-R system might be implicated in the processes of neuroprotection and restructuring (such as angiogenesis and gliosis) after ischemia. To support this hypothesis, a significant reduction in infarct volume (47%; P < 0.0002) was found in mice treated with recombinant Epo 24 hours before induction of cerebral ischemia. Based on the above, we propose that the Epo/Epo-R system is an endogenous mechanism that protects the brain against damages consequent to a reduction in blood flow, a mechanism that can be amplified by the intracerebroventricular application of exogenous recombinant Epo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Blotting, Western
  • Brain / cytology
  • Brain Chemistry / physiology
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Cell Death / drug effects
  • Cells, Cultured
  • Cerebral Infarction / drug therapy
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / pathology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Erythropoietin / administration & dosage
  • Erythropoietin / biosynthesis*
  • Erythropoietin / pharmacology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Injections, Intraventricular
  • Mice
  • Neurons / drug effects
  • Receptors, Erythropoietin / biosynthesis*


  • Receptors, Erythropoietin
  • Erythropoietin