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Open AccessArticle

Temporal Characterization of Blood–Brain Barrier Disruption with High-Frequency Electroporation

1
Bioelectromechanical Systems Laboratory, School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA
2
Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA
3
Department of Small Animal Clinical Sciences, Virginia Tech, Blacksburg, VA 24061, USA
4
Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(12), 1850; https://doi.org/10.3390/cancers11121850
Received: 5 November 2019 / Revised: 21 November 2019 / Accepted: 22 November 2019 / Published: 23 November 2019
Treatment of intracranial disorders suffers from the inability to accumulate therapeutic drug concentrations due to protection from the blood–brain barrier (BBB). Electroporation-based therapies have demonstrated the capability of permeating the BBB, but knowledge of the longevity of BBB disruption (BBBD) is limited. In this study, we quantify the temporal, high-frequency electroporation (HFE)-mediated BBBD in an in vivo healthy rat brain model. 40 male Fisher rats underwent HFE treatment; two blunt tipped monopolar electrodes were advanced into the brain and 200 bursts of HFE were delivered at a voltage-to-distance ratio of 600 V/cm. BBBD was verified with contrast enhanced T1W MRI (gadopentetate dimeglumine) and pathologically (Evans blue dye) at time points of 1, 24, 48, 72, and 96 h after HFE. Contrast enhanced T1W scans demonstrated BBBD for 1 to 72 h after HFE but intact BBB at 96 h. Histologically, tissue damage was restricted to electrode insertion tracks. BBBD was induced with minimal muscle contractions and minimal cell death attributed to HFE. Numerical modeling indicated that brief BBBD was induced with low magnitude electric fields, and BBBD duration increased with field strength. These data suggest the spatiotemporal characteristics of HFE-mediated BBBD may be modulated with the locally applied electric field. View Full-Text
Keywords: blood–brain barrier disruption; electric field threshold; Evans blue dye; high-frequency electroporation; focal therapy; gadopentetate dimeglumine; electropermeabilization; numerical modeling; BBB disruption temporal threshold; transient BBB disruption blood–brain barrier disruption; electric field threshold; Evans blue dye; high-frequency electroporation; focal therapy; gadopentetate dimeglumine; electropermeabilization; numerical modeling; BBB disruption temporal threshold; transient BBB disruption
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MDPI and ACS Style

Lorenzo, M.F.; Thomas, S.C.; Kani, Y.; Hinckley, J.; Lee, M.; Adler, J.; Verbridge, S.S.; Hsu, F.-C.; Robertson, J.L.; Davalos, R.V.; Rossmeisl, J.H., Jr. Temporal Characterization of Blood–Brain Barrier Disruption with High-Frequency Electroporation. Cancers 2019, 11, 1850. https://doi.org/10.3390/cancers11121850

AMA Style

Lorenzo MF, Thomas SC, Kani Y, Hinckley J, Lee M, Adler J, Verbridge SS, Hsu F-C, Robertson JL, Davalos RV, Rossmeisl JH Jr.. Temporal Characterization of Blood–Brain Barrier Disruption with High-Frequency Electroporation. Cancers. 2019; 11(12):1850. https://doi.org/10.3390/cancers11121850

Chicago/Turabian Style

Lorenzo, Melvin F.; Thomas, Sean C.; Kani, Yukitaka; Hinckley, Jonathan; Lee, Matthew; Adler, Joy; Verbridge, Scott S.; Hsu, Fang-Chi; Robertson, John L.; Davalos, Rafael V.; Rossmeisl, John H., Jr. 2019. "Temporal Characterization of Blood–Brain Barrier Disruption with High-Frequency Electroporation" Cancers 11, no. 12: 1850. https://doi.org/10.3390/cancers11121850

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