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Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice-Feasibility Demonstration
Shirley Sharabi1, David Last1, Dianne Daniels1
1The Advanced Technology Center, Sheba Medical Center, Tel Hashomer, Ramat-Gan 5262000, Israel.
Pharmaceutics
|January 30, 2021
Summary
Low pulsed electrical fields (PEFs) non-invasively disrupt the blood-brain barrier (BBB) in mice. This method offers a promising approach for delivering therapeutics to the central nervous system.
Area of Science:
- Neuroscience
- Biophysics
- Medical Imaging
Background:
- The blood-brain barrier (BBB) restricts drug delivery to the brain, hindering central nervous system (CNS) disorder treatments.
- Developing safe and effective methods for BBB disruption (BBBd) is crucial for advancing CNS therapeutics.
Purpose of the Study:
- To investigate the efficacy of low pulsed electrical fields (PEFs) for inducing BBBd in a mouse model.
- To evaluate the relationship between PEF parameters and the extent of BBBd.
Main Methods:
- Mice were treated with low PEFs using trans-skull electrodes, varying pulse parameters (voltage, frequency, duration).
- BBB disruption was assessed using MRI-based treatment response assessment maps (TRAMs) and Evans blue extravasation.
- A 3D finite element model simulated electric field distribution and thermal effects.
Main Results:
- PEFs successfully induced immediate BBBd in mice.
- Significant linear correlations were observed between PEF parameters and the degree of BBBd.
- Simulations confirmed electric field distribution and negligible temperature increase, with maximal fields ranging from 62.4 to 187.2 V/cm.
Conclusions:
- Non-invasive low PEFs can effectively induce significant BBBd.
- This technique is feasible and operates below the electroporation threshold, suggesting a safe therapeutic window.
