Abstract:

Objective To investigate the effects of erythropoietin (EPO) on expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB）mRNA and protein after brain injury induced by ibotenic acid (Ibo) in mice of different developmental stages. Methods One hundred and twenty KM mice aged 7 d (n=40), 21 d (n=40) and 42 d (n=40) were selected, and those of the same age were randomly divided into Ibo group (n=15), Ibo+EPO group (n=15) and control group (n=10), respectively. In Ibo group, 1 μL Ibo was injected into left hippocampus. In Ibo+EPO group, intraperitoneal injection of 5 000 U/（kg·d）EPO was performed for 5 consecutive days after injection of 1 μL Ibo into left hippocampus. Mice in control group were treated with same amount of normal saline. Y-maze tests were carried out 5 d after model establishment in each group, the pathological changes of neurons in hippocampus were observed with Cresyl Violet staining, the expression of BDNF mRNA and TrkB mRNA in hippocampus was detected by Real-Time PCR, and the expression of BDNF protein and TrkB protein was determined by ELISA. Results After operation, the percentage of mice entering safe arm in Ibo group was significantly lower than that in control group （P<0.05）, while the percentage of mice entering safe arm in EPO+Ibo group was significantly higher than that in Ibo group (P<0.05). Light microscopy revealed that degeneration and cell death of neurons in hippocampus occurred in  Ibo group, and the death rates of neurons in hippocampus in Ibo+EPO group and Ibo group were significantly higher than that in control group （P<0.05）. However, the pathological changes of Ibo+EPO group were more moderate. The expression of BDNF and TrkB mRNA and protein in Ibo group and Ibo+EPO group was significantly higher than that in control group (P<0.05）, and the expression of BDNF and TrkB mRNA and protein in Ibo+EPO group was significantly higher than that in Ibo group (P<0.05）. Conclusion The expression of BDNF and TrkB mRNA and protein is significantly up-regulated in hippocampus of mice with Ibo-induced brain injury, which may be a protective reaction. EPO mitigates brain injury induced by Ibo, the mechanism of which may be related to the up-regulation of expression of BDNF and TrkB mRNA and protein.

Key words: brain-derived neurotrophic factor, tyrosine receptor kinase B, erythropoietin, ibotenic acid, brain damage, mouse