Temporal Characterization of Blood-Brain Barrier Disruption with High-Frequency Electroporation. 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. Cancers (Basel), 2019. 2072-6694 Lorenzo, Melvin F Orcid: 0000-0002-6518-5398 Thomas, Sean C Kani, Yukitaka Hinckley, Jonathan Orcid: 0000-0001-9868-1163 Lee, Matthew Adler, Joy Verbridge, Scott S Hsu, Fang-Chi Robertson, John L Davalos, Rafael V Orcid: 0000-0003-1503-9509 Rossmeisl, John H Jr Orcid: 0000-0003-1655-7076 R01CA213423/NH/NIH HHS/United States P01CA207206/NH/NIH HHS/United States Journal Article Switzerland 2019/11/28 Cancers (Basel). 2019 Nov 23;11(12):1850. doi: 10.3390/cancers11121850.
doi  abstract   bibtex   
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.
@article{RN140,
   author = {Lorenzo, M. F. and Thomas, S. C. and Kani, Y. and Hinckley, J. and Lee, M. and Adler, J. and Verbridge, S. S. and Hsu, F. C. and Robertson, J. L. and Davalos, R. V. and Rossmeisl, J. H., Jr.},
   title = {Temporal Characterization of Blood-Brain Barrier Disruption with High-Frequency Electroporation},
   journal = {Cancers (Basel)},
   volume = {11},
   number = {12},
   note = {2072-6694
Lorenzo, Melvin F
Orcid: 0000-0002-6518-5398
Thomas, Sean C
Kani, Yukitaka
Hinckley, Jonathan
Orcid: 0000-0001-9868-1163
Lee, Matthew
Adler, Joy
Verbridge, Scott S
Hsu, Fang-Chi
Robertson, John L
Davalos, Rafael V
Orcid: 0000-0003-1503-9509
Rossmeisl, John H Jr
Orcid: 0000-0003-1655-7076
R01CA213423/NH/NIH HHS/United States
P01CA207206/NH/NIH HHS/United States
Journal Article
Switzerland
2019/11/28
Cancers (Basel). 2019 Nov 23;11(12):1850. doi: 10.3390/cancers11121850.},
   abstract = {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.},
   keywords = {BBB disruption temporal threshold
Evans blue dye
blood–brain barrier disruption
electric field threshold
electropermeabilization
focal therapy
gadopentetate dimeglumine
high-frequency electroporation
numerical modeling
transient BBB disruption},
   ISSN = {2072-6694 (Print)
2072-6694},
   DOI = {10.3390/cancers11121850},
   year = {2019},
   type = {Journal Article}
}

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