Action of brain-derived neurotrophic factor on brain damage induced by status convulsion in rats

Objective To investigate whether the exogenous BDNF or the phosphorylation of cAMP response element-binding protein(pCREB) influence the hippocampal BDNF expression and the apoptotic procedure in vivo.Methods Seizures were induced in ARs with lithium and pilocarpine injected intraperitoneally. The rats were intraventricular (IV) injected with BDNF or anti-pCREB antibody after SC, and sacrificed 1 d later. The levels of BDNF in both hippocampi were determined by quantitative ELISA(pg·μg-1). The apoptotic cells was quantified by the Annexin V-FITC apoptosis detection. The expression of pCREB in hippocampus 30 min after SC was observed by semiquantitative immunohistochemistry.Results ①In the normal control group, there was no significant alteration for BDNF levels in the lateral received IVI NS or anti-pCREB antibody, but the BDNF level in the lateral received IVI-BDNF was much higher than that in the non-IVI group and NS-IVI group(P0.01).The expression of BDNF was obviously increased in rat hippocampus after SC(P0.01). The administration of IVI NS did not cause marked change of BDNF levels in the lateral received IVI after SC. The level of BDNF in the hippocampus of the lateral received IVI BDNF (0.4 μg)was significantly increased in the normal group and SC group, and was much higher in SC group (55.40±4.11) compared with the normal group(P0.01).Among the SC experimental groups, the BDNF levels were the highest in BDNF-IVI group. The level of BDNF in the lateral received IVI anti-pCREB antibody( 400 μg) was dropped dramatically(P0.01)in the SC group compared with that in the other SC experimental group(non-IVI control group, NS-IVI group, BDNF-IVI group, P0.01)and that in the blank control group(P0.05). In the lateral received IVI anti-pCREB antibody in the normal group , BDNF level was not significantly increased compared with the blank control (5.94±0.60, 5.91±1.63, respectively).The intraventricular injection(NS or BDNF) had no significant influence on BDNF expression in the contralateral in the normal group or SC group. The intraventricular injection of anti-pCREB antibody could induce the decrease of BDNF expression in the contralateral after SC. ② In the normal control group, the proportion of apoptotic cells in the lateral received IVI was remarkably higher than that in the the blank control (P0.01). The neuronal apoptosis in hippocampus had no positive correlation with injection .Compared to the time point before SC, the proportion of apoptotic cells in the hippocampus was increased obviously at d1 after SC .After SC , the proportion of apoptotic cells in the lateral treated was remarkably higher than that in the non-IVI control group (P0.01). The proportions of apoptotic cells were different because of the three kinds of injectants. The proportion of apoptotic cells in the lateral received IVI was (8.36±0.61)% after IVI NS. The proportion of apoptotic cells was (4.10±1.00)% after IVI BDNF ,which was remardedly lower than that after IVI NS. The proportion of apoptotic cells was (9.37±2.50)% after IVI anti-pCREB antibody ,which was higher than that after IVI NS.The patterns of neuronal apoptosis in the contralateral were similar to that in the lateral treated . Whether in the normal condition or after SC, the severity degree of apoptosis in the contralateral was less than that in the lateral treated.Conclusions ①The exogenous BDNF could induce the expression of endogenous BDNF and partly inhibit neuronal apoptosis in the lateral hippocampus with intraventricular injection. ② The blockade of CREB phosphorylation induced the apoptotic procedure, probably through suppressing the BDNF expression.