Beneficial effect of erythropoietin on sensorimotor function and white matter after hypoxia-ischemia in neonatal mice.
There are mixed reports on the neuroprotective properties of erythropoietin (EPO) in animal models of birth asphyxia. We investigated the effect of EPO on short- and long-term outcome after neonatal hypoxic-ischemic (HI) brain injury in mice and compared the effect of two different dose regimens of EPO. Nine-day-old mice were subjected to HI, and EPO was injected i.p. at 0, 24, and 48 h after HI in a dose of either 5 or 20 kU/kg. Paw preference in the cylinder rearing test (CRT) was used as a measure of sensorimotor function. Only in female mice, administration of EPO at 5 kU/kg but not 20 kU/kg improved sensorimotor function, reduced striatum atrophy and hippocampal lesion volume, and enhanced myelin basic protein (MBP) staining as determined at 4 and 9 wk after HI. In addition, at 72 h after HI, more Ki 67 cells were found in the subventricular zone and dentate gyrus after EPO 5 kU/kg treatment, indicating an increase in progenitor cell proliferation. In conclusion, EPO improves sensorimotor function after neonatal HI and protects against striatum atrophy, hippocampus injury, and white matter loss. The protective effect of EPO is dose-dependent and only present in females.
Fan
Xiyong
X
Department of Neonatology, University Medical Center Utrecht, Utrecht 3584EA, The Netherlands.
Heijnen
Cobi J
CJ
van der KOOIJ
Michael A
MA
Groenendaal
Floris
F
van Bel
Frank
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology*; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D012737:Sex Factors; D013997:Time Factors
D004676:Myelin Basic Protein; D004921:Erythropoietin