Expression changes of brain-derived neurotrophic factors in cortex and hippocampus after hypoxia-ischemia injury in immature rats / 中华实用儿科临床杂志

ABSTRACT

Objective To study the effect of hypoxia-ischemia (HI) on the brain-derived neurotrophic factor (BDNF) expression in the brain cortex and the hippocampus of immature rats,and to provide new therapeutic strategies for HI brain injury.Methods Three-day-old rats were divided into 2 groups.One group of rat pups were subjected to the left carotid artery ligation followed by 60 mL/L oxygen for 2.5 hours(HI-treated rats).The other group of rat pups were only subjected to the left carotid artery separation without ligation and 60 mL/L oxygen (sham-treated rats).The brain tissues were prepared at 3,7 and 14 d after treatment.Cresyl fast videt(CV) staining was used to evaluate the damage of the cortex and the hippocampus and check whether the models were successfully made.Immunostaining was used to determine the changes in BDNF positive cells in the brain cortex and the hippocampus after HI.Western blot analysis was used to evaluate the expression of BDNF protein in the brain cortex and the hippocampus after HI.Results Models were successfully made.CV staining showed that there was brain damages and area loss in the cortex and the hippocampus after HI.BDNF immunostaining showed that the number of BDNF-positive cells was significantly decreased in the cortex (t =-3.225,-2.298,all P ＜ 0.05) and the hippocampus (t =-3.751,-2.920,all P ＜ 0.05) in the damaged side of the brain compared to the contralateral side in the rats treated with HI and the sham-treated rats at 3 d after surgery,while increased at 7 d(t =3.924,2.838,all P ＜ 0.05 for cortex ; t =4.136,2.256,all P ＜0.05 for hippocampus) and 14 d (t =3.256,2.624,all P ＜ 0.05 for cortex ; t =3.051,2.719,all P ＜ 0.05 for hippocampus) after surgery.Western blot analysis showed protein expressions of BDNF(1) Hippocampusthe protein expressions of BDNF were significantly decreased in damaged side of the brain compared to the contralateral side of rats treated with HI at 3 d(t =-3.388,P ＜ 0.05) after surgery,while increased compared to the contralateral side of rats treated with HI and the sham-treated rats at 14 d(t =4.874,4.646,all P ＜0.05) after surgery.(2)Cortexthe protein expression of BDNF was significantly decreased in damaged side of the brain compared to the contralateral side of rats treated with HI and the sham-treated rats at 3 d(t =-7.386,-3.256,all P ＜ 0.05) after surgery,compared to the sham-treated rats at 7 d(t =4.439,P ＜ 0.05) and the contralateral side of rats treated with HI and the sham-treated rats 14 d(t =24.161,3.942,all P ＜ 0.05) after surgery.Conclusions The number of BDNF-positive cells and protein expressions are decreased in the cortex and the hippocampus at the early stage of HI injury,and increased at the late stage.BDNF may play a role in the healing stage of HI brain injury.