Influence of Long-term Treatment of Phenobarbital and Topiramate on Bcl-2 and Bax Protein in Brain Tissue of Young Rats

Objective To investigate the influence of long-term treatment of phenobarbital( PB) and topiramate( TPM) on Bcl-2 and Bax protein in brain tissue of young rats. Methods A total of 60 healthy 18-day-old SD young rats were randomly divided into normal control group,PB group,TPM group,20 in each. Each group was further devided into long-term( 4 weeks) treated group and short-term( 2 weeks) treated group randomly,10 in each. The rats in PB group were given intragastric administration with PB 30 mg·kg-1·d-1,the rats in TPM group were given intragastric administration with TPM 40 mg·kg-1·d-1,and the rats in normal control group were given intragastric administration with equal volume of 0. 9% sodium chloride solution. The body and brain weight were measured when the rats were sacrificed after 2 weeks and 4 weeks, brain tissue was embedded in paraffin,hematoxylin-eosin staining and Nissl staining used,changes in brain tissue obversed by light microscope morphological,expression of apoptosis-related proteins Bcl-2 and Bax in neurons detected by immunohistochemistry. Results There were no significant differences in body weights,brain weights and histological changes among short PB administration group,short TPM administration group and normal control group( P 0. 05). The brain weights in long-term treated group of PB was significantly reduced compared with the normal control group( P 0. 01),prefrontal cortical neurons decreased and neuronal structures had obvious abnormalities. The body weights,brain weights and structural changes in the long-term treated group of TPM were without statistically significant difference compared with normal control group( P 0. 05). The rats brain frontal cortex Bax protein and Bax/Bcl-2 ratio in long-term treated groups of PB was higher than those of normal control group( P 0. 05). There was no statistical significance in the Bax protein and Bax/Bcl-2 ratio between long-term treated group of TPM and normal control group( P 0. 05). Conclusion Long-term treatment of PB will result in significant neuronal apoptosis,necrosis,persistent cognitive impairment and brain damage to immature rats. The expression of Bax protein in the frontal lobe and the high rate of Bax/Bcl-2 were probably the main reason that brain weights decreased and brain damaged by PB in immature rats. Long-term treatment of TPM is without obvious changes in brain structure.