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Article

Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration

1
The Advanced Technology Center, Sheba Medical Center, Tel Hashomer, Ramat-Gan 5262000, Israel
2
Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Ramat-Gan 5262000, Israel
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Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
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The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel
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Department of Pharmacology, Institute for Drug Research, Hebrew University, Jerusalem 9112001, Israel
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Institute for Health and Medical Professions, Department of Sports Therapy, Ono Academic College, Kiryat Ono 5545173, Israel
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Interdisciplinary Center Herzliya, Herzliya 4610101, Israel
*
Author to whom correspondence should be addressed.
Academic Editor: Xavier Declèves
Pharmaceutics 2021, 13(2), 169; https://doi.org/10.3390/pharmaceutics13020169
Received: 26 November 2020 / Revised: 6 January 2021 / Accepted: 23 January 2021 / Published: 27 January 2021
(This article belongs to the Special Issue Drug Delivery to Brain Tumors)
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. View Full-Text
Keywords: blood–brain barrier disruption; pulsed electrical fields; MRI; treatment response assessment maps; non-invasive; neurodegenerative diseases blood–brain barrier disruption; pulsed electrical fields; MRI; treatment response assessment maps; non-invasive; neurodegenerative diseases
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MDPI and ACS Style

Sharabi, S.; Last, D.; Daniels, D.; Fabian, I.D.; Atrakchi, D.; Bresler, Y.; Liraz-Zaltsman, S.; Cooper, I.; Mardor, Y. Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration. Pharmaceutics 2021, 13, 169. https://doi.org/10.3390/pharmaceutics13020169

AMA Style

Sharabi S, Last D, Daniels D, Fabian ID, Atrakchi D, Bresler Y, Liraz-Zaltsman S, Cooper I, Mardor Y. Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration. Pharmaceutics. 2021; 13(2):169. https://doi.org/10.3390/pharmaceutics13020169

Chicago/Turabian Style

Sharabi, Shirley; Last, David; Daniels, Dianne; Fabian, Ido D.; Atrakchi, Dana; Bresler, Yael; Liraz-Zaltsman, Sigal; Cooper, Itzik; Mardor, Yael. 2021. "Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice—Feasibility Demonstration" Pharmaceutics 13, no. 2: 169. https://doi.org/10.3390/pharmaceutics13020169

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