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.
(c) 2009 S. Karger AG, Basel.