Effects of mutant erythropoietin on neurogenesis and angiogenesis after cerebral ischemia in mice

doi:10.3969/j.issn.1009-6574.2016.06.007

Abstract：Objective To investigate the effects of novel nonerythropoietic mutant erythropoietin (mEPO) on neurogenesis and angiogenesis after middle cerebral artery occlusion in mice.Methods Totals of 30 adult male C57BL/B6 mice were randomly divided into Sham group (n =10),I/R+ Veh group (n =10) and I/R+mEPO group (n =10).Mice in I/R+mEPO group and I/R+Veh group were treated with mEPO (5 000 IU/kg) or isovolumetric saline after transient middle cerebral artery occlusion (MCAO).Cell proliferation was detected by bromodeoxyuridine (BrdU),while neurological function was assessed progressively by Rota-rod test.Mice were euthanized 14 days after injury and reperfusion (I/R) for evaluation of brain tissue loss volume,neurogenesis and angiogenesis.Results Proportion of brain tissue loss volume in I/R + mEPO group was significantly lower than I/R + Veh group [(14.62 ± 5.80) ％ vs (29.81±7.75) ％,P ＜0.05].Neural function in I/R+mEPO group improved significantly in 3d and 7d after cerebral ischemia and returned to normal after 7 d (P ＜0.05).Numbers of BrdU+/NeuN+ cells (36.25±10.53) and BrdU+/Laminin+ cells (25.25± 6.34) in I/R+mEPO group were significantly higher than Sham group and I/R+Veh group (P ＜ 0.05).Conclusions mEPO can promote focal neurogenesis and angiogenesis,and attenuate ischemia-induced brain injury in mice after MCAO.Therefore nonerythropoietic mutant EPO is a potential drug for ischemic stroke therapy.