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1- Department of Anatomy, Institute of Medical Education and Research, Chandigarh-160012, India.
2- Department of Biochemistry, Singh Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh-160012, India.
3- Department of Neurosurgery, Institute of Medical Education and Research, Chandigarh-160012, India.
4- Department of Neurology, Institute of Medical Education and Research, Chandigarh-160012, India.
5- Department of Forensic Medicine, Institute of Medical Education and Research, Chandigarh-160012, India.
6- Department of Histopathology, Institute of Medical Education and Research, Chandigarh-160012, India.
Abstract:  
About 30% of epileptic patients do not react 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. We have studied these two transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). 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. The study demonstrated that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy.
Type of Study: Original | Subject: Cellular and molecular Neuroscience
Received: 2021/06/29 | Accepted: 2021/08/9

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