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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...

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Autores principales: Sharabi, Shirley, Last, David, Daniels, Dianne, Fabian, Ido Didi, Atrakchi, Dana, Bresler, Yael, Liraz-Zaltsman, Sigal, Cooper, Itzik, Mardor, Yael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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