Mutant Erythropoietin Promotes Neurogenesis And Angiogenesis After Middle Cerebral Artery Occlusion In Mice

Objective:To investigates a novel nonerythropoietic mutant erythropoietin(mEPO)and its potential neuroprotective effects on neurogenesis and angiogenesis in mice after cerebral ischemia.Methods:Total 30 adult male C57 BL/B6 mice were treated with mEPO(5000IU/kg)orvehicleaftertransientmiddlecerebralarteryocclusion(MCAO).Neurological function was assessed progressively by Rota-rod test.Mice were euthanized 14 days after injury and reperfusion(I/R)for evaluation of brain tissuelossvolume,neurogenesis,andneuronalreplacementusing bromodeoxyuridine(BrdU)incorporation.Results:mEPO treatment significantly improved neurobehavioral outcomes(P<0.05).The numbers of BrdU~+/NeuN~+and BrdU~+/Laminin~+cells in the pri-infarction zone were increased in I/R+mEPO group compared to the I/R+Veh group(P<0.05).Similarly,immunohistochemical staining showed that microvessel density in the same region of mEPO-treated mice was significantly increased compared to the I/R+Veh group(P<0.01).The mEPO-enhanced remodeling in the ischemic hemisphere correlated with decreased brain tissue loss volume(P<0.05).Conclusion:mEPO promoted focal neurogenesis and angiogenesis,and attenuated ischemia-induced brain injury in mice after MCAO,suggesting that the nonerythropoietic mutant EPO is a potential drug for ischemic stroke therapy.