The effects of intraventricular administration of insulin on neuronal apoptosis in neonate rat after hypoxic-ischemic brain damage

Objective To investigate the effect of insulin on the neuronal apoptosis in neonate rat after hypoxic-ischemic encephalopathy(HIE).Methods We established HIE model based on Rice-Vanncci method in Sprague-Dawlay(SD)neonatal rats.Fifteen SD rats were randomly divided into insulin-treating group and control group.Lowdose insulin(1IU/kg)or phosphate-buffered saline(PBS)was injected intracˉerebroventricularly in treating group and control group respectively2hours after HIE.Apoptotic neurons in cortex and hippocampus were observed24hours after HIE by transmission electron microscope.Apoptotic neurons in cortex and hippocampus were counted by TUNEL(TdTmediated dUTP nick end labeling)method24hours after HIE.Caspase-3P20subunit in brain tissue was checked by Western-blot24hours after HIE.Blood sugar was checked90minutes after intracerebroventricular injectionl.Results The apoptotic neurons was less frequent in insulin group than that in control under transmission electron microscope.Quantitative neuropathology with TUNEL method showed that the apoptosis neurons in cortex and hippocampus of insulin treating group were less than that of control(t=6.940and5.855,P0.01).Ninety minutes after intraventricular injection,the blood sugar levels were not different between two groups(t=0.733,P0.05).Twenty four hours after HI,the ID of Caspase-3P20subunit by western-blot in insulin-treating group was less than that of control group(w=24.00,P0.05).Conclusion Insulin provides neuroproptection after HIE in neonate possibly by reducing neuronal apoptosis,which may be associated with the inhibition of Caspase-3activation.