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

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dc.contributor.authorLorenzo, Melvin F.en
dc.contributor.authorThomas, Sean C.en
dc.contributor.authorKani, Yukitakaen
dc.contributor.authorHinckley, Jonathanen
dc.contributor.authorLee, Matthewen
dc.contributor.authorAdler, Joyen
dc.contributor.authorVerbridge, Scott S.en
dc.contributor.authorHsu, Fang-Chien
dc.contributor.authorRobertson, John L.en
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorRossmeisl, John H. Jr.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentSmall Animal Clinical Sciencesen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessioned2019-12-16T13:53:43Zen
dc.date.available2019-12-16T13:53:43Zen
dc.date.issued2019-11-23en
dc.date.updated2019-12-09T08:27:46Zen
dc.description.abstractTreatment 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLorenzo, 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.en
dc.identifier.doihttps://doi.org/10.3390/cancers11121850en
dc.identifier.urihttp://hdl.handle.net/10919/95992en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectblood–brain barrier disruptionen
dc.subjectelectric field thresholden
dc.subjectEvans blue dyeen
dc.subjecthigh-frequency electroporationen
dc.subjectfocal therapyen
dc.subjectgadopentetate dimeglumineen
dc.subjectelectropermeabilizationen
dc.subjectnumerical modelingen
dc.subjectBBB disruption temporal thresholden
dc.subjecttransient BBB disruptionen
dc.titleTemporal Characterization of Blood–Brain Barrier Disruption with High-Frequency Electroporationen
dc.title.serialCancersen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Collections

Journal Articles, Multidisciplinary Digital Publishing Institute (MDPI)
Destination Area: Adaptive Brain and Behavior (ABB)
Scholarly Works, Biomedical Engineering and Mechanics
Scholarly Works, School of Biomedical Engineering and Sciences
Scholarly Works, Small Animal Clinical Sciences