Role of Permeability glycoprotein (P-gp) and Multidrug resistance
protein 1 (MRP-1) in drug-resistance in mesial temporal lobe epilepsy
Abstract
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 protein-1 (MRP-1). We have
studied these two transporters in the sclerotic hippocampal tissues
resected from the epilepsy surgery and compared their expression profile
with the tissues resected from non-epileptic autopsy cases.
Statistically significant over expression of both P-gp
(p-value<0.0001) and MRP-1 (p-value 0.01) at gene and protein
levels was found in the MTLE cases. The fold change of P-gp was more
pronounced than MRP-1. Immunohistochemistry of patient group showed
increased immunoreactivity of P-gp at blood brain barrier and increased
reactivity of MRP-1 in parenchyma. The results were confirmed by
confocal immunofluorescence microscopy. This suggested that P-gp in
association with MRP-1 might be responsible for the multi-drug
resistance in epilepsy.