Sandra Veronica Lopez-Quintero and Abhishek Datta
In this study, we investigated whether DBS relevant electric fields will increase transport across endothelial monolayers. A novel system was developed for generating controlled uniform electric fields across confluent BAECS monolayers.
Schematic of customized stimulation system
A microporous membrane insert with confluent cell layers was placed inside the stimulation chamber. Uniform electric fields were generated was passing current between two Ag/AgCl electrodes. The chmaber can be used to continuously monitor effects of stimulation on monolayer haydraulic permeability (electropermeation) and individual cell loading and death after stimulation (electroporation).
Electric fields induced during DBS
Finite element model (FEM) of peak tissue electric field during 3V activation of electrodes 1 and 4 on Medtronic Lead 3387. These electric field magnitudes are reproduced in vitro across the BAECS monolayers.
No significant electroporation was observed after 5 minutes of stimulation with fields up to 2.5 V/cm. The figure below shows the barrier electropermeation results.
Water flux values were normalized to the value at t=60 min, right before the electric field was applied for 5 min. The increased permeability is related to the amplitude of the electric field. No cell death was observed in these trials.
Our results suggest that clinical levels of electric fields used in DBS could result in loss of endothelial barrier function (electropermeation) not linked to single cell electroporation or cell death. ZO-1 staining revealed a punctuate and a discontinuous pattern for electropermeated monolayers.
Further in vivo validation is warranted to address barrier electropermeation during DBS.