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Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration
The blood–brain barrier (BBB) is a major hurdle for the treatment of central nervous system disorders, limiting passage of both small and large therapeutic agents from the blood stream into the brain. Thus, means for inducing BBB disruption (BBBd) are urgently needed. Here, we studied the applicatio...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911365/ https://www.ncbi.nlm.nih.gov/pubmed/33513968 http://dx.doi.org/10.3390/pharmaceutics13020169 |
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author | Sharabi, Shirley Last, David Daniels, Dianne Fabian, Ido Didi Atrakchi, Dana Bresler, Yael Liraz-Zaltsman, Sigal Cooper, Itzik Mardor, Yael |
author_facet | Sharabi, Shirley Last, David Daniels, Dianne Fabian, Ido Didi Atrakchi, Dana Bresler, Yael Liraz-Zaltsman, Sigal Cooper, Itzik Mardor, Yael |
author_sort | Sharabi, Shirley |
collection | PubMed |
description | The blood–brain barrier (BBB) is a major hurdle for the treatment of central nervous system disorders, limiting passage of both small and large therapeutic agents from the blood stream into the brain. Thus, means for inducing BBB disruption (BBBd) are urgently needed. Here, we studied the application of low pulsed electrical fields (PEFs) for inducing BBBd in mice. Mice were treated by low PEFs using electrodes pressed against both sides of the skull (100–400 square 50 µs pulses at 4 Hz with different voltages). BBBd as a function of treatment parameters was evaluated using MRI-based treatment response assessment maps (TRAMs) and Evans blue extravasation. A 3D numerical model of the mouse brain and electrodes was constructed using finite element software, simulating the electric fields distribution in the brain and ensuring no significant temperature elevation. BBBd was demonstrated immediately after treatment and significant linear regressions were found between treatment parameters and the extent of BBBd. The maximal induced electric field in the mice brains, calculated by the numerical model, ranged between 62.4 and 187.2 V/cm for the minimal and maximal applied voltages. These results demonstrate the feasibility of inducing significant BBBd using non-invasive low PEFs, well below the threshold for electroporation. |
format | Online Article Text |
id | pubmed-7911365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79113652021-02-28 Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration Sharabi, Shirley Last, David Daniels, Dianne Fabian, Ido Didi Atrakchi, Dana Bresler, Yael Liraz-Zaltsman, Sigal Cooper, Itzik Mardor, Yael Pharmaceutics Article The blood–brain barrier (BBB) is a major hurdle for the treatment of central nervous system disorders, limiting passage of both small and large therapeutic agents from the blood stream into the brain. Thus, means for inducing BBB disruption (BBBd) are urgently needed. Here, we studied the application of low pulsed electrical fields (PEFs) for inducing BBBd in mice. Mice were treated by low PEFs using electrodes pressed against both sides of the skull (100–400 square 50 µs pulses at 4 Hz with different voltages). BBBd as a function of treatment parameters was evaluated using MRI-based treatment response assessment maps (TRAMs) and Evans blue extravasation. A 3D numerical model of the mouse brain and electrodes was constructed using finite element software, simulating the electric fields distribution in the brain and ensuring no significant temperature elevation. BBBd was demonstrated immediately after treatment and significant linear regressions were found between treatment parameters and the extent of BBBd. The maximal induced electric field in the mice brains, calculated by the numerical model, ranged between 62.4 and 187.2 V/cm for the minimal and maximal applied voltages. These results demonstrate the feasibility of inducing significant BBBd using non-invasive low PEFs, well below the threshold for electroporation. MDPI 2021-01-27 /pmc/articles/PMC7911365/ /pubmed/33513968 http://dx.doi.org/10.3390/pharmaceutics13020169 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sharabi, Shirley Last, David Daniels, Dianne Fabian, Ido Didi Atrakchi, Dana Bresler, Yael Liraz-Zaltsman, Sigal Cooper, Itzik Mardor, Yael Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration |
title | Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration |
title_full | Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration |
title_fullStr | Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration |
title_full_unstemmed | Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration |
title_short | Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration |
title_sort | non-invasive low pulsed electrical fields for inducing bbb disruption in mice—feasibility demonstration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911365/ https://www.ncbi.nlm.nih.gov/pubmed/33513968 http://dx.doi.org/10.3390/pharmaceutics13020169 |
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