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 () and multidrug-resistance associated protein-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 and 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<0.0001) and (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of was more pronounced than . Immunohistochemistry of the patient group showed increased immunoreactivity of at blood-brain barrier and increased reactivity of in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy.

Conclusion: Our results suggested that in association with might be responsible for the multi-drug resistance in epilepsy. and 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.