Non-invasive low pulsed electrical fields for inducing BBB disruption in mice—feasibility demonstration

Shirley Sharabi*, David Last, Dianne Daniels, Ido Didi Fabian, Dana Atrakchi, Yael Bresler, Sigal Liraz-Zaltsman, Itzik Cooper, Yael Mardor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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 soft-ware, 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.

Original languageAmerican English
Article number169
Pages (from-to)1-15
Number of pages15
JournalPharmaceutics
Volume13
Issue number2
DOIs
StatePublished - 27 Jan 2021

Bibliographical note

Publisher Copyright:
© 2021 by the au-thors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Blood–brain barrier disruption
  • MRI
  • Neurodegenerative diseases
  • Non-invasive
  • Pulsed electrical fields
  • Treatment response assessment maps

Fingerprint

Dive into the research topics of 'Non-invasive low pulsed electrical fields for inducing BBB disruption in mice—feasibility demonstration'. Together they form a unique fingerprint.

Cite this