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Role of Permeability glycoprotein (P-gp) and Multidrug resistance protein 1 (MRP-1) in drug-resistance in mesial temporal lobe epilepsy
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  • Mandeep Kaur,
  • Tulika Gupta,
  • Mili Gupta,
  • Navneet Singla,
  • Parampreet Singh,
  • Yogendra Bansal,
  • B.D. Radotra,
  • S.K. Gupta
Mandeep Kaur
Post Graduate Institute of Medical Education and Research
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Tulika Gupta
Post Graduate Institute of Medical Education and Research
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Mili Gupta
Panjab University
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Navneet Singla
Post Graduate Institute of Medical Education and Research
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Parampreet Singh
Post Graduate Institute of Medical Education and Research
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Yogendra Bansal
Post Graduate Institute of Medical Education and Research
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B.D. Radotra
Post Graduate Institute of Medical Education and Research
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S.K. Gupta
Post Graduate Institute of Medical Education and Research
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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.