title: Erythropoietin sustains cognitive function and brain volume after neonatal stroke.
abstract: 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.
authors: Department of Pediatrics, University of California, San Francisco, CA 94143-0663, USA. gonzalezf@peds.ucsf.edu
authors: Fernando F
authors: FF
authors: Gonzalez
authors: Regina
authors: R
authors: Abel
authors: C Robert
authors: CR
authors: Almli
authors: Dezhi
authors: D
authors: Mu
authors: Michael
authors: M
authors: Wendland
authors: Donna M
authors: DM
authors: Ferriero
mesh_terms: 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
chemical_list: D004921:Erythropoietin