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Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery

Resected hippocampal tissue from patients with drug-resistant epilepsy presents a unique possibility to test novel treatment strategies directly in target tissue. The post-resection time for testing and analysis however is normally limited. Acute tissue slices allow for electrophysiological recordin...

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Autores principales: Wickham, J., Brödjegård, N. G., Vighagen, R., Pinborg, L. H., Bengzon, J., Woldbye, D. P. D., Kokaia, M., Andersson, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841387/
https://www.ncbi.nlm.nih.gov/pubmed/29515159
http://dx.doi.org/10.1038/s41598-018-22554-9
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author Wickham, J.
Brödjegård, N. G.
Vighagen, R.
Pinborg, L. H.
Bengzon, J.
Woldbye, D. P. D.
Kokaia, M.
Andersson, M.
author_facet Wickham, J.
Brödjegård, N. G.
Vighagen, R.
Pinborg, L. H.
Bengzon, J.
Woldbye, D. P. D.
Kokaia, M.
Andersson, M.
author_sort Wickham, J.
collection PubMed
description Resected hippocampal tissue from patients with drug-resistant epilepsy presents a unique possibility to test novel treatment strategies directly in target tissue. The post-resection time for testing and analysis however is normally limited. Acute tissue slices allow for electrophysiological recordings typically up to 12 hours. To enable longer time to test novel treatment strategies such as, e.g., gene-therapy, we developed a method for keeping acute human brain slices viable over a longer period. Our protocol keeps neurons viable well up to 48 hours. Using a dual-flow chamber, which allows for microscopic visualisation of individual neurons with a submerged objective for whole-cell patch-clamp recordings, we report stable electrophysiological properties, such as action potential amplitude and threshold during this time. We also demonstrate that epileptiform activity, monitored by individual dentate granule whole-cell recordings, can be consistently induced in these slices, underlying the usefulness of this methodology for testing and/or validating novel treatment strategies for epilepsy.
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spelling pubmed-58413872018-03-14 Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery Wickham, J. Brödjegård, N. G. Vighagen, R. Pinborg, L. H. Bengzon, J. Woldbye, D. P. D. Kokaia, M. Andersson, M. Sci Rep Article Resected hippocampal tissue from patients with drug-resistant epilepsy presents a unique possibility to test novel treatment strategies directly in target tissue. The post-resection time for testing and analysis however is normally limited. Acute tissue slices allow for electrophysiological recordings typically up to 12 hours. To enable longer time to test novel treatment strategies such as, e.g., gene-therapy, we developed a method for keeping acute human brain slices viable over a longer period. Our protocol keeps neurons viable well up to 48 hours. Using a dual-flow chamber, which allows for microscopic visualisation of individual neurons with a submerged objective for whole-cell patch-clamp recordings, we report stable electrophysiological properties, such as action potential amplitude and threshold during this time. We also demonstrate that epileptiform activity, monitored by individual dentate granule whole-cell recordings, can be consistently induced in these slices, underlying the usefulness of this methodology for testing and/or validating novel treatment strategies for epilepsy. Nature Publishing Group UK 2018-03-07 /pmc/articles/PMC5841387/ /pubmed/29515159 http://dx.doi.org/10.1038/s41598-018-22554-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wickham, J.
Brödjegård, N. G.
Vighagen, R.
Pinborg, L. H.
Bengzon, J.
Woldbye, D. P. D.
Kokaia, M.
Andersson, M.
Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery
title Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery
title_full Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery
title_fullStr Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery
title_full_unstemmed Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery
title_short Prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery
title_sort prolonged life of human acute hippocampal slices from temporal lobe epilepsy surgery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841387/
https://www.ncbi.nlm.nih.gov/pubmed/29515159
http://dx.doi.org/10.1038/s41598-018-22554-9
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