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Adenosine A1 receptor-mediated suppression of carbamazepine-resistant seizure-like events in human neocortical slices.

Authors :
Klaft, Zin ‐ Juan
Hollnagel, Jan ‐ Oliver
Salar, Seda
Calişkan, Gürsel
Schulz, Steffen B.
Schneider, Ulf C.
Horn, Peter
Koch, Arend
Holtkamp, Martin
Gabriel, Siegrun
Gerevich, Zoltan
Heinemann, Uwe
Source :
Epilepsia (Series 4); May2016, Vol. 57 Issue 5, p746-756, 11p
Publication Year :
2016

Abstract

Objective The need for alternative pharmacologic strategies in treatment of epilepsies is pressing for about 30% of patients with epilepsy who do not experience satisfactory seizure control with present treatments. In temporal lobe epilepsy ( TLE) even up to 80% of patients are pharmacoresistant, and surgical resection of the ictogenic tissue is only possible for a minority of TLE patients. In this study we investigate purinergic modulation of drug-resistant seizure-like events ( SLEs) in human temporal cortex slices. Methods Layer V/ VI field potentials from a total of 77 neocortical slices from 17 pharmacoresistant patients were recorded to monitor SLEs induced by application of 8 mM [K<superscript>+</superscript>] and 50 μ m bicuculline. Results Activating A<subscript>1</subscript> receptors with a specific agonist completely suppressed SLEs in 73% of human temporal cortex slices. In the remaining slices, incidence of SLEs was markedly reduced. Because a subportion of slices can be pharmacosensitive, we tested effects of an A<subscript>1</subscript> agonist, in slices insensitive to a high dose of carbamazepine (50 μ m). Also in these cases the A<subscript>1</subscript> agonist was equally efficient. Moreover, ATP and adenosine blocked or modulated SLEs, an effect mediated not by P2 receptors but rather by adenosine A<subscript>1</subscript> receptors. Significance Selective activation of A<subscript>1</subscript> receptors mediates a strong anticonvulsant action in human neocortical slices from pharmacoresistant patients. We propose that our human slice model of seizure-like activity is a feasible option for future studies investigating new antiepileptic drug ( AED) candidates. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00139580
Volume :
57
Issue :
5
Database :
Complementary Index
Journal :
Epilepsia (Series 4)
Publication Type :
Academic Journal
Accession number :
115229983
Full Text :
https://doi.org/10.1111/epi.13360