Erythropoietin sustains cognitive function and brain volume after neonatal stroke.
Neonatal stroke leads to mortality and severe morbidity, but there currently is no effective treatment. Erythropoietin (EPO) promotes cytoprotection and neurogenesis in the short term following brain injury; however, long-term cognitive outcomes and optimal dosing regimens have not been clarified. We performed middle cerebral artery occlusion in postnatal day 10 rats, which were treated with either a single dose of EPO (5 U/g, i.p.) immediately upon reperfusion, or 3 doses of EPO (1 U/g, i.p. each) at 0 h, 24 h, and 7 days after injury. At 3 months after injury, rats treated with 3 doses of EPO did not differ from shams in the Morris water maze, and generally performed better than either rats treated with a single dose or vehicle-treated injured rats. These multiple-dose-treated rats also had increases in hemispheric volume and its subregions. These results suggest that additional, later doses of EPO may be required for cell repair, proliferation, and long-term incorporation into neural networks after neonatal brain injury.
Gonzalez
Fernando F
FF
Department of Pediatrics, University of California, San Francisco, CA 94143-0663, USA. gonzalezf@peds.ucsf.edu
Abel
Regina
R
Almli
C Robert
CR
Mu
Dezhi
D
Wendland
Michael
M
Ferriero
Donna M
DM
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects*; D019610:Cytoprotection; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D008279:Magnetic Resonance Imaging; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects
D004921:Erythropoietin