Abstract: Abstract: Objective To investigate the effects of seizure and/or an antiepileptic drug Carbamazepine (CBZ) on expression of P-glycoprotein (P-gp) encoded by a multidrug resistance gene. Methods Female SD rats were intracerebroventricularly injected with kainate (KA) and/or orally administered with CBZ or PBS. The animals were deeply anesthetized and perfused 3 d, 5 d, 7 d, 14 d, 21 d and 28 d after seizure or 7 d, 14 d, 21 d and 28 d after CBZ administration, and their brain was removed. Immunohistochemistry and double lebeling immunostaining were used for semiqualification analysis and location of P-gp in the brain, and Nissl staining was used to observe neuronal alterations in the hippocampus. Results The changes in EEG and behavior in the model rats were the same as those in human epilepsy. CBZ was weakly against the seizure generated by KA. Five days after seizure, P-gp expression in the hippocampus began to increase significantly and reached to its peak level at 7 d (P<0.001), then returned to the control level 21 d later. The immunopositive products were mainly present in the capillary endothelia in the hippocampus and also in the endothelia and neurons in the cortex. CBZ interference showed no effects on expression of P-gp compared with those in the PBS-injected rats. The changes in P-gp expression in KA+CBZ group were the same as those observed in the KA model rat, however, its P-gp expression at 7 d was stronger than that in the KA group. Conclusions Seizure may induce over-expression of P-gp, and CBZ may be involved in up-regulation of P-gp expression in the KA model rat.

Key words: Intractable epilepsy, P-glycoprotein, Kainate, Carbamazepine