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

Autor: Shirley Sharabi, David Last, Dianne Daniels, Ido Didi Fabian, Dana Atrakchi, Yael Bresler, Sigal Liraz-Zaltsman, Itzik Cooper, Yael Mardor
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Pharmaceutics, Vol 13, Iss 2, p 169 (2021)
Druh dokumentu: article
ISSN: 1999-4923
99434644
DOI: 10.3390/pharmaceutics13020169
Popis: 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.
Databáze: Directory of Open Access Journals
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