expressional study of permeability glycoprotein and multidrug resistance protein 1 in drug-resistant mesial temporal lobe epilepsy

Introduction: about 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. the pathogenesis of drug-resistance in mesial temporal lobe epilepsy (mtle) is not completely understood. increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. the major drug-efflux transporters are permeability glycoprotein (p-gp) and multidrug-resistance associated protein-1 (mrp-1). the major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue.methods: we have studied p-gp and mrp-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15).results: statistically significant over expression of both p-gp (p<0.0001) and mrp-1 (p=0.01) at gene and protein levels were found in the mtle cases. the fold change of p-gp was more pronounced than mrp-1. immunohistochemistry of the patient group showed increased immunoreactivity of p-gp at blood-brain barrier and increased reactivity of mrp-1 in the parenchyma. the results were confirmed by confocal immunofluorescence microscopy.conclusion: our results suggested that p-gp in association with mrp-1 might be responsible for the multi-drug resistance in epilepsy. p-gp and mrp-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.