The Study Of Expression Of P-Glycoprotein In Chronic Epileptic Rat And Effect Of Verapamile

Epilepsy is a common chronic and often progressive neurological disorder, affecting approximately 1-2% of the population. Despite having newly approved antiepileptic drugs (AEDs), about 30% of patients are refractory to the treatment. An important characteristic of pharmacoresistant epilepsy is that most patients with refractory epilepsy are resistant to several drugs with different mechanisms. The phenomenon is similar to that in tumors. The recent finding of multidrug transporters, such as P-glycoprotein in the endothelial cells of the blood-brain barrier, is of particular interest since these outwardly directed active efflux mechanisms appear to act as an active defense mechanism of limiting brain accumulation of many lipophilic drugs. When P-glycoprotein overexpresses, it can result in the decrease of drugs. In the normal brain, P-glycoprotein is expressed in capillary endothelial cells, but cannot be detected by routine immunohistochemistry in brain parenchyma, i.e, astrocytes or neurons. In the pathological circumstance, P-glycoprotein can be detected in astrocytes and neurons. Overexpression of P-glycopreotein is influenced by many factors, such as epileptic degree and antiepileptic drugs; however, the underlying mechanisms are unclear. Therefore, we established a chronic epileptic rat model to measure the expression of P-glycoprotein, investigate the relationship of P-glycoprotein, seizure and antiepileptic drugs, evaluate the regulatory function of carbamazepine at the extracellular level, and also examine the effect of P-glycoprotein inhibitor. We hope to find a new strategy for refractory epileptic patients.1. Establishment of a chronic epileptic rat model(1) Objective: To establish a chronic epileptic rat model and examine the effect of carbamazepine on kindling process.