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

The present study describes, for the first time, a temporal and spatial cel lular 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 postisch emic 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 hypothe sis that there is a continuous formation of Epo, with its corresponding rec eptor, during the active evolution of a focal cerebral infarct and that the Epo/Epo-R system might be implicated in the processes of neuroprotection a nd restructuring (such as angiogenesis and gliosis) after ischemia. To supp ort this hypothesis, a significant reduction in infarct volume (47%; P < 0. 0002) was found in mice treated with recombinant Epo 24 hours before induct ion 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.