The Effect Of Colivelin In Ischemic Brain Injury

Background and Purpose: Colivelin belongs to humanin family with potent capacity to rescue neuronal death associated with Alzheimer's disease.We seek to investigate the effects Colivelin on ischemic brain injury and mechanism underlying the Colivelin-mediated action on ischemic neurons.Methods: We adopted 60 min induction of transient focal cerebral ischemia and reperfusion in mice.Mice were treated with either vehicle(20% ethyl alcohol)or 1mg/kg Colivelin intraperitoneally daily,from day 0 for continuous 6 days.Infarct volume and neurological deficits were evaluated until 14 days.Neuronal apoptosis was assessed by TUNEL staining and apoptosis gene array panel.Biotinylated dextran amine(BDA)was injected into contralesional cortex to anterogradely label the corticospinal tract for accessing axonal remodeling.JAK2/STAT3 expression and phosphorylation were measured by western blot.Results: Relative to mice received vehicle,Colivelin administration decreased the neurological deficits and infarct lesion induced by brain ischemia.Colivelin inhibited axonal damage and neuronal death in brain tissues of MCAO mice,which was associated with increased anti-apoptotic genes expression in injured neuron.Further,Colivelin activated STAT3 signaling,which may contribute to its beneficial effect of against neuronal death and axon remodeling.Conclusions: These results illustrate that Colivelin induce anti-apoptotic genes,activate JAK2/STAT3,which may contribute to its effects of rescuing ischemic neuronal death and axonal remodeling.This study may justify further works to examine Colivelin as a single or adjunct therapy in ischemic stroke.