The role of p38 in the apoptosis of hippocampal CA1 neurons after cerebral ischemia/reperfusion

Objective To investigate the mechanism of p38 regulating apoptosis on CA1 neurons after cerebral ischemia/reperfusion(I/R). Methods Using 4-vessel occlusion(4-VO) as brain ischemia model. Forty-eight Adult SD female rats were bilaterally ovariectomized. After ovariectomized 7 day, the rats were randomly assigned into Sham group, I/R group, vehicle control group(Vehicle group) and p38 inhibitor group(p38-I group). Vehicle group and p38-I group rats were given 10 μl 1% dimethyl sulfoxide(DMSO) and SB203580(100 μmol/L) by intracerebroventricular injection 20 min before ischemia respectively. Western blot and immunoprecipitation were used to examine changes of phosphorylation of Bcl-2, interaction between Bcl-2 and Bax, Bax protein mitochondrial translocation in rat hippocampal CA1 regions. In addition, cresyl-violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Results Compared with rats in the I/R group, the level of phosphorylate Bcl-2(p-Bcl-2) protein was significantly decreased. Interaction between Bcl-2 and Bax, Bax from mitochondria to cytoplasm of hippocampal CA1 regions of rats in the p38-I group was significantly increased(P<0.05). But the total amount of Bcl-2 and Bax proteins had no significant changes. Cresyl-violet staining showed that the neuronal apoptosis of hippocampal CA1 regions of rats in the p38-I group was significantly reduced(P<0.05). Conclusions p38 inhibitor could inhibit the apoptosis of rat hippocampal CA1 neurons. This effect might be achieved by reducing the Bcl-2 phosphorylation level, increasing interaction between Bcl-2 and Bax and the translocation of Bax from the mitochondria to the cytosol. Key words: p38 inhibitor; Ischemia/reperfusion; Bax; Hippocampus