MDR1 Gene Expression in Brain of Patients with Medically Intractable Epilepsy

• DOI: 10.1111/j.1528-1157.1995.tb01657.x
• Publication Date: 2005-08-03T16:58:12Z
• Authors: David M. Tishler; Kenneth I. Weinberg; David R. Hinton; Nicholas Barbaro; Geralyn M. Annett; Corey Raffel
• Keywords: P-glycoprotein; Efflux; Drug Resistant Epilepsy

Why some patients with seizures are successfully treated antiepileptic drugs (AEDs) and others prove medically intractable is not known. Inadequate intraparenchymal drug concentration a possible mechanism of resistance to AEDs. The multiple gene (MDR1) encodes P-glycoprotein, an energy-dependent efflux pump that exports planar hydrophobic molecules from the cell. If P-glycoprotein expressed in brain epilepsy AEDs exported by lower concentrations could contribute lack response such patients. Eleven 19 specimens removed during operation for had MDR1 mRNA levels > 10 times greater than those normal brain, as determined quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Immunohistochemistry 14 showed increased staining capillary endothelium samples epileptic compared samples. In high levels, expression astrocytes also was identified. Last, steady-state intracellular phenytoin (PHT) expressing neuroectodermal cells one fourth MDR1-negative cells. epilepsy, suggesting patients' medication may be caused inadequate accumulation AED brain.