A potential role for erythropoietin in focal permanent cerebral ischemia in mice.
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.
Bernaudin
M
M
Université de Caen, UMR 6551-CNRS, France.
Marti
H H
HH
Roussel
S
S
Divoux
D
D
Nouvelot
A
A
MacKenzie
E T
ET
Petit
E
E
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000166:cytology; D001923:Brain Chemistry / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000096:biosynthesis* / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D051379:Mice; D009474:Neurons / Q000187:drug effects; D017467:Receptors, Erythropoietin / Q000096:biosynthesis*
D017467:Receptors, Erythropoietin; D004921:Erythropoietin