Perampanel attenuates epileptiform phenotype in C6 glioma. (10th January 2020)

• Record Type: Journal Article
• Authors: Mayer, Johannes; Kirschstein, Timo; Resch, Tobias; Porath, Katrin; Krause, Bernd Joachim; Köhling, Rüdiger; Lange, Falko
• Is Part Of: Neuroscience letters. Volume 715(2020)
• Publication Date: 2020-01-10
• Subjects: Glioma -- Epilepsy -- Perampanel -- Glutamate -- AMPA receptor; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2019.134629
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: In this study, we investigate the effects of AMPA receptor antagonist perampanel for the first time in a C6 glioma model. Perampanel attenuated glucose uptake but did not affect glutamate level in C6 glioma cultures. In rats no survival benefit by perampanel in a monotherapy setting was achieved. Also, tumor size was not reduced. Epileptiform discharges can be inhibited by perampanel, underline its potential as an effective anticonvulsant in glioma. Abstract: Epileptic seizures are frequent in patients with glioma, and anticonvulsive treatment is often indicated. Glioma cells release glutamate via the Xc - antiporter system, which appears to be a major pathomechanism of glioma-associated seizures and excitotoxicity. In addition, the proliferation and survival of the tumor cells are promoted. Therefore, anticonvulsants that attenuate glutamate-mediated receptor activation could be especially effective. In this study, we investigated the effects of AMPA receptor antagonist perampanel in rat C6 glioma model. In first pilot experiments, perampanel reduced glucose uptake but had no impact of extracellular glutamate level in vitro . To analyze the effects of perampanel in vivo, we injected C6 cells orthotopically into the neocortex of Wistar rats in order to establish a model of glioma-associated epilepsy. Spontaneous recurrent discharges in brain slices were abolished upon perfusion with the AMPA receptor blocker perampanel, supporting the major role of glutamatergic excitation. With respect to the tumor progression, no effect of perampanel on survival of the animals or on glioma size was determined. Our data demonstrate that perampanel inhibit epileptiform discharges in organotypic brain slices of glioma, but failed to attenuate tumor growth or promote animal survival.