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Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model

An abnormal glutamate signaling of glioblastoma may contribute to both tumor progression and the generation of glioma-associated epileptic seizures. We hypothesized that the AMPA receptor antagonist perampanel (PER) could attenuate tumor growth and epileptic events. F98 glioma cells, grown orthotopi...

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Autores principales: Lange, Falko, Hartung, Jens, Liebelt, Clara, Boisserée, Julius, Resch, Tobias, Porath, Katrin, Hörnschemeyer, Julia, Reichart, Gesine, Sellmann, Tina, Neubert, Valentin, Kriesen, Stephan, Hildebrandt, Guido, Schültke, Elisabeth, Köhling, Rüdiger, Kirschstein, Timo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734300/
https://www.ncbi.nlm.nih.gov/pubmed/33328869
http://dx.doi.org/10.3389/fnins.2020.598266
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author Lange, Falko
Hartung, Jens
Liebelt, Clara
Boisserée, Julius
Resch, Tobias
Porath, Katrin
Hörnschemeyer, Julia
Reichart, Gesine
Sellmann, Tina
Neubert, Valentin
Kriesen, Stephan
Hildebrandt, Guido
Schültke, Elisabeth
Köhling, Rüdiger
Kirschstein, Timo
author_facet Lange, Falko
Hartung, Jens
Liebelt, Clara
Boisserée, Julius
Resch, Tobias
Porath, Katrin
Hörnschemeyer, Julia
Reichart, Gesine
Sellmann, Tina
Neubert, Valentin
Kriesen, Stephan
Hildebrandt, Guido
Schültke, Elisabeth
Köhling, Rüdiger
Kirschstein, Timo
author_sort Lange, Falko
collection PubMed
description An abnormal glutamate signaling of glioblastoma may contribute to both tumor progression and the generation of glioma-associated epileptic seizures. We hypothesized that the AMPA receptor antagonist perampanel (PER) could attenuate tumor growth and epileptic events. F98 glioma cells, grown orthotopically in Fischer rats, were employed as a model of glioma to investigate the therapeutic efficiency of PER (15 mg/kg) as adjuvant to standard radiochemotherapy (RCT). The epileptiform phenotype was investigated by video-EEG analysis and field potential recordings. Effects on glioma progression were estimated by tumor size quantification, survival analysis and immunohistological staining. Our data revealed that orthotopically-growing F98 glioma promote an epileptiform phenotype in rats. RCT reduced the tumor size and prolonged the survival of the animals. The adjuvant administration of PER had no effect on tumor progression. The tumor-associated epileptic events were abolished by PER application or RCT respectively, to initial baseline levels. Remarkably, PER preserved the glutamatergic network activity on healthy peritumoral tissue in RCT-treated animals. F98 tumors are not only a robust model to investigate glioma progression, but also a viable model to simulate a glioma-associated epileptiform phenotype. Furthermore, our data indicate that PER acts as a potent anticonvulsant and may protect the tumor-surrounding tissue as adjuvant to RCT, but failed to attenuate tumor growth or promote animal survival.
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spelling pubmed-77343002020-12-15 Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model Lange, Falko Hartung, Jens Liebelt, Clara Boisserée, Julius Resch, Tobias Porath, Katrin Hörnschemeyer, Julia Reichart, Gesine Sellmann, Tina Neubert, Valentin Kriesen, Stephan Hildebrandt, Guido Schültke, Elisabeth Köhling, Rüdiger Kirschstein, Timo Front Neurosci Neuroscience An abnormal glutamate signaling of glioblastoma may contribute to both tumor progression and the generation of glioma-associated epileptic seizures. We hypothesized that the AMPA receptor antagonist perampanel (PER) could attenuate tumor growth and epileptic events. F98 glioma cells, grown orthotopically in Fischer rats, were employed as a model of glioma to investigate the therapeutic efficiency of PER (15 mg/kg) as adjuvant to standard radiochemotherapy (RCT). The epileptiform phenotype was investigated by video-EEG analysis and field potential recordings. Effects on glioma progression were estimated by tumor size quantification, survival analysis and immunohistological staining. Our data revealed that orthotopically-growing F98 glioma promote an epileptiform phenotype in rats. RCT reduced the tumor size and prolonged the survival of the animals. The adjuvant administration of PER had no effect on tumor progression. The tumor-associated epileptic events were abolished by PER application or RCT respectively, to initial baseline levels. Remarkably, PER preserved the glutamatergic network activity on healthy peritumoral tissue in RCT-treated animals. F98 tumors are not only a robust model to investigate glioma progression, but also a viable model to simulate a glioma-associated epileptiform phenotype. Furthermore, our data indicate that PER acts as a potent anticonvulsant and may protect the tumor-surrounding tissue as adjuvant to RCT, but failed to attenuate tumor growth or promote animal survival. Frontiers Media S.A. 2020-11-30 /pmc/articles/PMC7734300/ /pubmed/33328869 http://dx.doi.org/10.3389/fnins.2020.598266 Text en Copyright © 2020 Lange, Hartung, Liebelt, Boisserée, Resch, Porath, Hörnschemeyer, Reichart, Sellmann, Neubert, Kriesen, Hildebrandt, Schültke, Köhling and Kirschstein. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Lange, Falko
Hartung, Jens
Liebelt, Clara
Boisserée, Julius
Resch, Tobias
Porath, Katrin
Hörnschemeyer, Julia
Reichart, Gesine
Sellmann, Tina
Neubert, Valentin
Kriesen, Stephan
Hildebrandt, Guido
Schültke, Elisabeth
Köhling, Rüdiger
Kirschstein, Timo
Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model
title Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model
title_full Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model
title_fullStr Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model
title_full_unstemmed Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model
title_short Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model
title_sort perampanel add-on to standard radiochemotherapy in vivo promotes neuroprotection in a rodent f98 glioma model
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734300/
https://www.ncbi.nlm.nih.gov/pubmed/33328869
http://dx.doi.org/10.3389/fnins.2020.598266
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