ABC transporter expression in drug-resistant epilepsy

Authors

• LD Weidner
• P Kannan
• MD Hall
• RB Innis
• WH Theodore
• J Mulder

Abstract

Background Thirty percent of epileptics have drug resistant epilepsy (DRE). The upregulation of the blood-brain barrier efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) is thought to underlie DRE. Many studies have measured P-gp in brain tissue samples from patients with DRE and found increased expression. The tissue used for these studies are obtained from resection surgeries of the seizure focus. There have been multiple reports classifying this tissue based on the level of sclerosis. Therefore, we sought to determine whether P-gp/BCRP expression is dependent on the level of sclerosis within DRE brain samples. In addition, we compared P-gp/BCRP expression to specific inflammatory markers to determine whether an increase in ABC transporter expression is observed in inflamed tissue. By comparing P-gp/BCRP expression within the epilepsy tissue samples themselves, it eliminates the need for post-mortem control tissue. We also utilized a new method of quantification, which correlates the expression of P-gp and BCRP to blood vessel density, providing a more reliable measure of expression. Methods We obtained surgical tissue samples from patients with mesial temporal lobe epilepsy, and post-mortem tissue from patients with AIDs or multiple sclerosis, and healthy controls. Using immunofluorescence techniques, we measured the expression of the ABC transporters, P-gp and BCRP, as well as the pro-inflammatory markers cyclooxygenase (COX)-1, -2, and translocator protein (TSPO) to correlate to the amount of P-gp/BCRP expression. To determine the localization of COX-1, -2, and TSPO, we stained for GFAP-positive astrocytes, microglia, and macrophages. Results TBD Conclusion TBD

Scientific Focus Area: Neuroscience

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