Erythropoietin enhances long-term neuroprotection and neurogenesis in neonatal stroke.
Neonatal stroke leads to mortality and severe morbidity, but there is no effective treatment currently available. Erythropoietin (EPO) has been shown to promote cytoprotection and neurogenesis and decrease subventricular zone morphologic changes following brain injury. The long-term cellular response to EPO has not been defined, and local changes in cell fate decision may play a role in functional improvement. We performed middle cerebral artery occlusion in P10 rats. EPO treatment (5 U/g i.p.) significantly preserved hemispheric brain volume 6 weeks after injury. Furthermore, EPO increased the percentage of newly generated neurons while decreasing newly generated astrocytes following brain injury, without demonstrating long-term differences in the subventricular zone. These results suggest that EPO may neuroprotect and direct cell fate toward neurogenesis and away from gliogenesis in neonatal stroke.
Gonzalez
Fernando F
FF
Department of Pediatrics, University of California, San Francisco, Calif. 94143-0663, USA. gonzalezf@peds.ucsf.edu
McQuillen
Patrick
P
Mu
Dezhi
D
Chang
Yunsil
Y
Wendland
Michael
M
Vexler
Zinaida
Z
Ferriero
Donna M
DM
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D005911:Gliosis / Q000517:prevention & control; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013995:Time; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D004921:Erythropoietin