Expression Of P-glycoprotein And Multidrug-resistance Protein 1 And ECoG In A Kindling Model Induced By Coriaria Lactone

Purpose: The aim of this study was to explore the possiblepharmacoresistant mechanism by developing a kindling model of Sprague-Dawley rats induced by Coriaria lactone (CL).Method: 60 Sprague-Dawley rats were randomized into test group(n=55)and control group(n=5). The test group received repeated CL injection at subthreshold dosage every 84 hours a time, totally 30 times, and the control group received normal saline (NS). The kindled rats received AEDs treatment, that is the maximal human adult dosage of carbamazepine (CBZ), valproate (VPA), and topiramate (TPM)(n =6 for each group), and NS (n=5) administered as monotherapy to different groups of kindled rats for 1 month. Before and after therapy, changes of seizure number, intensity (expressed as grade 1-5 according to Racine stage) were compared, and the expressions of P-glycoprotein, multidrug resistance-associated protein 1 (MRP1) by immunohistochemistry staining tissues in brain samples from different groups of experimental rats were observed occasionally.Result: A total of 23 (41.8%) rats were fully kindled. Electrocorticogram (ECoG) was observed which was consistant with the behavioral changes. Theseizure conditions of kindled rats changed little(P=0.683), and the expressions of P-gp, MRP1 in temporal lobe and hippocampus increased compared with the control and unkindled group (P=0.000).Conclusion: The study provided an ideal animal kindling model ofpharmacoresistant epilepsy induced by CL. The increased expressions of P-gp, MRP1 in temporal lobe and hippocampus might involve in induction of the pharmacoresistance.