Drug resistance in cortical and hippocampal slices from resected tissue of epilepsy patients: no significant impact of p-glycoprotein and multidrug resistance-associated proteins

Frontiers in Neurology
Nora SandowU Heinemann

Abstract

Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp) and multidrug resistance-associated proteins (MRPs) expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs [carbamazepine (CBZ), sodium valproate, phenytoin] and two unspecific inhibitors of Pgp and MRPs [verapamil (VPM) and probenecid (PBN)] on seizure-like events (SLEs) induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices) were studied. Although in slice preparations the blood brain barrier is not functional, we found that SLEs predominantly persisted in the presence of anticonvulsant drugs (90%) and also in the presence of VPM and PBN (86%). Following subsequent co-administration of anti-epileptic drugs and drug transport inhibitors, SLEs continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30%) or as suppression (7%), particularly by perfusion with CBZ in PBN containing solutions (43, 9%)...Continue Reading

References

Nov 1, 1992·Annals of Neurology·M J During, D D Spencer
Jun 1, 1990·The Journal of Comparative Neurology·M J West, H J Gundersen
Jan 1, 1987·Electroencephalography and Clinical Neurophysiology·O W WitteJ Walden
Jul 2, 1998·Brain : a Journal of Neurology·R KöhlingF Oppel
Dec 2, 1999·Pediatric Neurology·A LazarowskiA Rabinowicz
Feb 24, 2001·Lancet·S M SisodiyaM Thom
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·S J Lee, B S McEwen
Aug 8, 2001·The European Journal of Neuroscience·T N LehmannU Heinemann
Dec 4, 2002·Epilepsia·Ali GorjiErwin-Joseph Speckmann
Apr 1, 2003·Annals of Neurology·Stefan RemyHeinz Beck
Aug 26, 2004·The Annals of Pharmacotherapy·Monica A SummersJames W McAuley
Nov 19, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Siegrun GabrielThomas-Nicolas Lehmann
Dec 4, 2004·Clinical Chemistry and Laboratory Medicine : CCLM·Hugo M NeelsWilly E Lambert
Dec 4, 2004·Clinical Chemistry and Laboratory Medicine : CCLM·Fritz PragstBjörn-Thoralf Erxleben
Jul 19, 2005·Nature Reviews. Neuroscience·Wolfgang Löscher, Heidrun Potschka
Dec 1, 2005·Brain : a Journal of Neurology·Stefan Remy, Heinz Beck
May 23, 2006·Pharmacological Reviews·Shannon DallasReina Bendayan
Sep 5, 2006·Brain : a Journal of Neurology·Katerina JandováThomas-Nicolas Lehmann
Oct 18, 2006·The Journal of Pharmacology and Experimental Therapeutics·Steffen BaltesWolfgang Löscher
Nov 25, 2006·Brain : a Journal of Neurology·E A van VlietJ A Gorter
Feb 24, 2007·Epilepsia·Heinz Beck
May 30, 2007·Brain : a Journal of Neurology·Valérie RigauMireille Lerner-Natoli

❮ Previous
Next ❯

Citations

Nov 17, 2015·Expert Review of Neurotherapeutics·Francesco NicitaParisi Pasquale
Aug 25, 2015·Journal of Neuroscience Methods·Leandro Leite AntonioUwe Heinemann
May 18, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Udo Bonnet, Martin Wiemann
Sep 26, 2019·Frontiers in Molecular Neuroscience·Larissa KrausPawel Fidzinski
Mar 26, 2021·BMC Biology·Sanja BojicJoão Pedro de Magalhães

❮ Previous
Next ❯

Software Mentioned

PASW statistics
Spike2
Kappa Image
SPSS

Related Concepts

Related Feeds

Blood-Brain Barrier Transport in Neurodegeneration

The blood brain barrier is important for regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the blood brain barrier can be essential for regulating drug movement and dysregulation of these processes may play a role in neurodegeneration. This feed follows the latest research on this topic.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.