Effects of erythropoietin on neuron apoptosis and expression of caspase-3 after excitotoxic brain injury in mice during different developmental stages

Objective To investigate the effects of erythropoietin (EPO) on neuron apoptosis and expression of caspase-3 after excitotoxic brain injury induced by ibotenic acid (Ibo) in mice during different developmental stages.Methods A total of 144 healthy KM mice aged 7 d (n =48),21 d (n =48) and 42 d (n =48) were selected,and those of the same age were randomly (random number) divided into 3 groups:sham surgery group (n =16),Ibo group (n =16) and EPO treated group (n =16).Brain injury model was established by Ibo 1μl (5 μg) injected into left hippocampus.In EPO treated group,intraperitoneal injection of 5000 U/ (kg · d) EPO was performed for 3 consecutive days after injection of 1 μl Ibo into left hippocampus.Mice in sham surgery group and Ibo control group were treated with saline in the same dose instead.The pathological changes of neurons in hippocampus were observed 3 d after modeling in each group with Nissl staining,the level and activity of caspase-3 in hippocampus were determined by ABCELISA and spectrophotometry.Result After modeling,degeneration and death of neurons in hippocampuswith substantially decrease in number of intact neurons were found under light microscopy in Ibo group in comparison with sham surgery group.However,compared with the Ibo group,pathological changes in EPO treated group were less serious.The level of caspase-3 in Ibo control group was significantly higher than that in sham surgery group (P＜0.05),and the level of caspase-3 in EPO treated group was significantly lower than that in Ibo group (P ＜ 0.05).Conclusions The level of caspase-3 is significantly up-regulated in hippocampus of mice with Ibo-induced brain injury,leading to neuron apoptosis.EPO mitigates brain injury and plays a role of protection on brain function,suggesting the mechanism is attributed to decrease in caspase-3. Key words: Erythropoietin;  Ibotenic acid;  Caspase-3;  Brain damage;  Apoptosis;  Mouse