The expression of hypoxia-inducible factor 1α and erythropoietin in hippocampus in hypoxia-ischemia neonatal rats

Objective To investigate the expression of hypoxia-inducible factor-1α(HIF-1α)and brain-derived erythropoietin(EPO)in the hippocampus following hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods HIBD animals group:the left common carotid artery of Sprague-Dawley rats were ligated 7 day postnatal(P7),then exposed to the hypoxic condition.Inducible hypoxia(iH)animal group:P7 rat pups were put under continous exposure of hypoxic condition for different period.Immunohistochemical staining was used to identify the expression of HIF-1α and EPO in the hippocampus at 0 h,1 h,6 h,16 h,1d,3 d,7 d in HIBD group.Immunohistochemical staining was also used to observe the expression of HIF-1α in inducible hypoxia group for 0.5 h,1 h,2 h,3 h,and 5 h.Results In hypoxia-ischemia group,EPO-immunoreactivity prolonged following re-oxygenation extension,reaching the peak at 16 h,and declined thereafter.The statistical difference was obvious(P0.001).There was no difference in the control group(P0.05).The expression of EPO was stronger in HIBD than that in control group.There was a certain amount of HIF-1α cell production in dentate gyrus while exposed to hypoxia-ischemia.When rats returned to normoxia condition(NC)and re-oxygenation,there was no HIF-1α expression.HIF-1α immunoreactivity was observed under continuous hypoxia exposure for 0.5 h.It was prominent under continuous hypoxia exposure for 3 h.There was no HIF-1α expression on normoxia condition.Conclusions HIF-1α is induced due to hypoxia.We postulate that HIF-1α/EPO hypoxic signal probably initiate hippocampal neurogenesis after HIBD.