Gliafunktionsänderungen in epileptischem Hirngewebe: Störung der glialen Kaliumpufferung

Zusammenfassung

Einleitung: Die pharmakoresistente mesiale Temporallappenepilepsie (mTLE) geht häufig mit einer Ammonshornsklerose (AHS) einher. Die AHS ist durch Verlust an Nervenzellen und strukturelle Veränderungen der Astrozyten (Gliose) charakterisiert. Wir vermuteten, dass diese Astrozyten ihre Fähigkeit verloren haben, Kaliumionen mittels bariumsensitiver K⁺-Kanäle aufzunehmen und umzuverteilen. Deshalb untersuchten wir die Wirkung von Barium auf evozierte Anstiege der extrazellulären Kaliumkonzentration (K⁺)_o im Hippokampusgewebe von Epilepsiepatienten, epileptischen Ratten und nichtepileptischen Kontrollratten. Methodik: Die Veränderungen evozierter K⁺-Signale durch Barium wurden mit Hilfe zweikanaliger K⁺-selektiver Referenz Mikroelektroden in der CA1-Region akuter Hirnschnitte aus Hippokampusresektaten mit und ohne AHS und aus dem Hippokampus von Ratten (mit chronischer Epilepsie [Pilokarpin-Modell], mit Kindling-Epilepsie und ohne Epilepsie) gemessen. Die Auslösung der Signale erfolgte durch repetitive elektrische Reizung des Alveus oder durch K⁺-Iontophorese. Ergebnisse: Barium verursachte eine Vergrößerung iontophoretisch evozierter K⁺-Signale in der CA1 von Kontrolltieren und von Hippokampusresektaten ohne AHS. Barium vergrößerte auch die durch antidrome Reizung ausgelösten K⁺-Signale in der nichtsklerotischen CA1 von Epilepsiepatienten, Ratten mit Kindling-Epilepsie und Kontrollratten. Im Gegensatz dazu war in der CA1 von Resektaten mit AHS und im Gewebe chronisch epileptischer Ratten der Bariumeffekt nicht nachweisbar bzw. stark verringert. Schlussfolgerungen: Der Bariumeffekt auf die evozierten K⁺-Signale reflektiert die gliale Pufferkapazität für die während neuronaler Aktivität freigesetzten Kaliumionen. Das Fehlen des Bariumeffektes bei humaner TLE mit AHS lässt auf eine Verminderung der glialen Pufferkapazität und damit auf eine mögliche Störung der K⁺-Regulation schließen.

Abstract

Introduction: Pharmacoresistant mesial temporal lobe epilepsy (mTLE) is frequently accompanied by Ammon's horn sclerosis (AHS), characterised by nerve cell loss and structural alteration of astrocytes („gliosis”). We supposed that such astrocytes may have lost their capability to take up and to redistribute potassium ions by barium-sensitive K⁺-channels, and hence we investigated the effects of barium on evoked rises of (K⁺)_o in hippocampal tissue of epilepsy patients, epileptic rats and control rats. Methods: Changes of evoked K⁺ signals by barium were measured using double-barrelled K⁺ selective reference microelectrodes placed into the CA1-region of brain slices from hippocampal specimens with and without AHS, from hippocampi of chronic epileptic rats (Pilocarpine-model), rats with Kindling epilepsy, or control rats. The K⁺ signals were elicited by repetitive electrical stimulation of the alveus or by K⁺ ionophoresis. Results: Barium caused an augmentation of ionophoretically evoked K⁺ signals in the CA1 pyramidal cell layer from control rats and from hippocampal specimens without AHS but not from those with AHS. Barium also augmented K⁺ signals elicited by antidromic stimulation in the non-sclerotic CA1 of epilepsy-patients, of rats with Kindling epilepsy, and control rats. In contrast, the barium effect was strongly reduced in the CA1 of hippocampal specimens with AHS and of hippocampal tissue of pilocarpine treated chronic epileptic rats. Conclusions: The effect of barium on evoked K⁺ signals reflects the glial K⁺ buffer capacity for potassium ions released during neuronal activity. The very small effect of barium on K⁺ signals in human TLE with AHS indicates a loss of buffer capacity and, thereby, a possible alteration of the K⁺ regulation.

Key words

Mesial temporal lobe epilepsy - K⁺ regulation - glia - hippocampus - CA1

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