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An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity

Brain tumours have significant impacts on patients’ quality of life, and current treatments have limited effectiveness. To improve understanding of tumour development and explore new therapies, researchers rely on experimental models. However, reproducing tumour-associated epilepsy (TAE) in these mo...

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Autores principales: Chong, Harvey K., Ma, Ziang, Wong, Kendrew Ka Chuon, Morokoff, Andrew, French, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605659/
https://www.ncbi.nlm.nih.gov/pubmed/37891819
http://dx.doi.org/10.3390/brainsci13101451
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author Chong, Harvey K.
Ma, Ziang
Wong, Kendrew Ka Chuon
Morokoff, Andrew
French, Chris
author_facet Chong, Harvey K.
Ma, Ziang
Wong, Kendrew Ka Chuon
Morokoff, Andrew
French, Chris
author_sort Chong, Harvey K.
collection PubMed
description Brain tumours have significant impacts on patients’ quality of life, and current treatments have limited effectiveness. To improve understanding of tumour development and explore new therapies, researchers rely on experimental models. However, reproducing tumour-associated epilepsy (TAE) in these models has been challenging. Existing models vary from cell lines to in vivo studies, but in vivo models are resource-intensive and often fail to mimic crucial features like seizures. In this study, we developed a technique in which normal rat organotypic brain tissue is implanted with an aggressive brain tumour. This method produces a focal invasive lesion that preserves neural responsiveness and exhibits epileptiform hyperexcitability. It allows for real-time imaging of tumour growth and invasion for up to four weeks and microvolume fluid sampling analysis of different regions, including the tumour, brain parenchyma, and peritumoral areas. The tumour cells expand and infiltrate the organotypic slice, resembling in vivo behaviour. Spontaneous seizure-like events occur in the tumour slice preparation and can be induced with stimulation or high extracellular potassium. Furthermore, we assess extracellular fluid composition in various regions of interest. This technique enables live cell confocal microscopy to record real-time tumour invasion properties, whilst maintaining neural excitability, generating field potentials, and epileptiform discharges, and provides a versatile preparation for the study of major clinical problems of tumour-associated epilepsy.
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spelling pubmed-106056592023-10-28 An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity Chong, Harvey K. Ma, Ziang Wong, Kendrew Ka Chuon Morokoff, Andrew French, Chris Brain Sci Article Brain tumours have significant impacts on patients’ quality of life, and current treatments have limited effectiveness. To improve understanding of tumour development and explore new therapies, researchers rely on experimental models. However, reproducing tumour-associated epilepsy (TAE) in these models has been challenging. Existing models vary from cell lines to in vivo studies, but in vivo models are resource-intensive and often fail to mimic crucial features like seizures. In this study, we developed a technique in which normal rat organotypic brain tissue is implanted with an aggressive brain tumour. This method produces a focal invasive lesion that preserves neural responsiveness and exhibits epileptiform hyperexcitability. It allows for real-time imaging of tumour growth and invasion for up to four weeks and microvolume fluid sampling analysis of different regions, including the tumour, brain parenchyma, and peritumoral areas. The tumour cells expand and infiltrate the organotypic slice, resembling in vivo behaviour. Spontaneous seizure-like events occur in the tumour slice preparation and can be induced with stimulation or high extracellular potassium. Furthermore, we assess extracellular fluid composition in various regions of interest. This technique enables live cell confocal microscopy to record real-time tumour invasion properties, whilst maintaining neural excitability, generating field potentials, and epileptiform discharges, and provides a versatile preparation for the study of major clinical problems of tumour-associated epilepsy. MDPI 2023-10-11 /pmc/articles/PMC10605659/ /pubmed/37891819 http://dx.doi.org/10.3390/brainsci13101451 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chong, Harvey K.
Ma, Ziang
Wong, Kendrew Ka Chuon
Morokoff, Andrew
French, Chris
An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity
title An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity
title_full An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity
title_fullStr An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity
title_full_unstemmed An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity
title_short An In Vitro Brain Tumour Model in Organotypic Slice Cultures Displaying Epileptiform Activity
title_sort in vitro brain tumour model in organotypic slice cultures displaying epileptiform activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605659/
https://www.ncbi.nlm.nih.gov/pubmed/37891819
http://dx.doi.org/10.3390/brainsci13101451
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