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Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices
The blood-brain barrier (BBB) is a tightly and actively regulated vascular barrier. Answering fundamental biological and translational questions about the BBB with currently available approaches is hampered by a trade-off between accessibility and biological validity. We report an approach combining...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886996/ https://www.ncbi.nlm.nih.gov/pubmed/36717572 http://dx.doi.org/10.1038/s41467-023-36070-6 |
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author | Hanafy, Amira Sayed Steinlein, Pia Pitsch, Julika Silva, Mariella Hurtado Vana, Natascha Becker, Albert J. Graham, Mark Evan Schoch, Susanne Lamprecht, Alf Dietrich, Dirk |
author_facet | Hanafy, Amira Sayed Steinlein, Pia Pitsch, Julika Silva, Mariella Hurtado Vana, Natascha Becker, Albert J. Graham, Mark Evan Schoch, Susanne Lamprecht, Alf Dietrich, Dirk |
author_sort | Hanafy, Amira Sayed |
collection | PubMed |
description | The blood-brain barrier (BBB) is a tightly and actively regulated vascular barrier. Answering fundamental biological and translational questions about the BBB with currently available approaches is hampered by a trade-off between accessibility and biological validity. We report an approach combining micropipette-based local perfusion of capillaries in acute brain slices with multiphoton microscopy. Micro-perfusion offers control over the luminal solution and allows application of molecules and drug delivery systems, whereas the bath solution defines the extracellular milieu in the brain parenchyma. Here we show, that this combination allows monitoring of BBB transport at the cellular level, visualization of BBB permeation of cells and molecules in real-time and resolves subcellular details of the neurovascular unit. In combination with electrophysiology, it permits comparison of drug effects on neuronal activity following luminal versus parenchymal application. We further apply micro-perfusion to the human and mouse BBB of epileptic hippocampi highlighting its utility for translational research and analysis of therapeutic strategies. |
format | Online Article Text |
id | pubmed-9886996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98869962023-02-01 Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices Hanafy, Amira Sayed Steinlein, Pia Pitsch, Julika Silva, Mariella Hurtado Vana, Natascha Becker, Albert J. Graham, Mark Evan Schoch, Susanne Lamprecht, Alf Dietrich, Dirk Nat Commun Article The blood-brain barrier (BBB) is a tightly and actively regulated vascular barrier. Answering fundamental biological and translational questions about the BBB with currently available approaches is hampered by a trade-off between accessibility and biological validity. We report an approach combining micropipette-based local perfusion of capillaries in acute brain slices with multiphoton microscopy. Micro-perfusion offers control over the luminal solution and allows application of molecules and drug delivery systems, whereas the bath solution defines the extracellular milieu in the brain parenchyma. Here we show, that this combination allows monitoring of BBB transport at the cellular level, visualization of BBB permeation of cells and molecules in real-time and resolves subcellular details of the neurovascular unit. In combination with electrophysiology, it permits comparison of drug effects on neuronal activity following luminal versus parenchymal application. We further apply micro-perfusion to the human and mouse BBB of epileptic hippocampi highlighting its utility for translational research and analysis of therapeutic strategies. Nature Publishing Group UK 2023-01-30 /pmc/articles/PMC9886996/ /pubmed/36717572 http://dx.doi.org/10.1038/s41467-023-36070-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Hanafy, Amira Sayed Steinlein, Pia Pitsch, Julika Silva, Mariella Hurtado Vana, Natascha Becker, Albert J. Graham, Mark Evan Schoch, Susanne Lamprecht, Alf Dietrich, Dirk Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices |
title | Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices |
title_full | Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices |
title_fullStr | Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices |
title_full_unstemmed | Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices |
title_short | Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices |
title_sort | subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886996/ https://www.ncbi.nlm.nih.gov/pubmed/36717572 http://dx.doi.org/10.1038/s41467-023-36070-6 |
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