Skip to main content
SpringerLink
Log in
Book cover

Handbook of Electroporation pp 1–17Cite as

Effect of Electroporation on Blood-Brain Barrier

  • Living reference work entry
  • First Online:

  • 261 Accesses

Abstract

The blood–brain barrier (BBB) is a multicellular vascular structure that separates the central nervous system (CNS) from the peripheral blood circulation. It forms the major obstacle for effective drug penetration into the brain, thus limiting extensively the efficacy of systemically administered therapeutic agents for treating brain tumors as well as neurodegenerative diseases.

Electroporation (EP)-induced BBB disruption is a novel technique that can be used for delivering high concentrations of therapeutic drugs to specific brain regions.

Electroporation is a technique in which intense electric pulses are applied to make the cell membrane transiently porous and increase permeability to ions and macromolecules. When applied to the brain, electroporation can also induce transient BBB disruption. The BBB can either be disrupted without causing irreversible damage to the brain or in combination with irreversible electroporation where BBB disruption surrounds a smaller irreversibly electroporated volume. The treatment can be performed in a minimally invasive manner using a single intracranial electrode or require craniotomy if multiple electrodes are used. It is possible to predict treatment outcome using statistical and computerized models describing the electrical field distribution in the brain.

Electroporation-induced localized BBB disruption lasts in the order of 24–48 h. The relatively long duration of the disruption differs from reversible electroporation which only lasts several minutes post treatment. The combination of electroporation-induced BBB disruption with systemic administration of therapeutic agent is suitable for treating primary or metastatic brain tumors as well as localized neurodegenerative diseases.

This is a preview of subscription content, log in via an institution.

References

  • Abbott NJ (2013) Blood–brain barrier structure and function and the challenges for CNS drug delivery. J Inherit Metab Dis 36(3):437–449. doi:10.1007/s10545-013-9608-0

    Article  MathSciNet  Google Scholar 

  • Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7(1):41–53. doi:10.1038/nrn1824

    Article  Google Scholar 

  • Corovic S, Lackovic I, Sustaric P, Sustar T, Rodic T, Miklavcic D (2013) Modeling of electric field distribution in tissues during electroporation. Biomed Eng Online 12:16. doi:10.1186/1475-925X-12-16

    Article  Google Scholar 

  • Garcia PA, Rossmeisl JH Jr, Neal RE 2nd, Ellis TL, Davalos RV (2011) A parametric study delineating irreversible electroporation from thermal damage based on a minimally invasive intracranial procedure. Biomed Eng Online 10:34. doi:10.1186/1475-925X-10-34

    Article  Google Scholar 

  • Garcia PA, Rossmeisl JH Jr, Robertson JL, Olson JD, Johnson AJ, Ellis TL, Davalos RV (2012) 7.0-T magnetic resonance imaging characterization of acute blood–brain-barrier disruption achieved with intracranial irreversible electroporation. PLoS One 7(11):e50482. doi:10.1371/journal.pone.0050482

    Article  Google Scholar 

  • Hjouj M, Last D, Guez D, Daniels D, Sharabi S, Lavee J, Rubinsky B, Mardor Y (2012) MRI study on reversible and irreversible electroporation induced blood brain barrier disruption. PLoS One 7(8), e42817. doi:10.1371/journal.pone.0042817

    Article  Google Scholar 

  • Jarm T, Cemazar M, Miklavcic D, Sersa G (2010) Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases. Expert Rev Anticancer Ther 10(5):729–746. doi:10.1586/era.10.43

    Article  Google Scholar 

  • Kranjc M, Markelc B, Baid F, Čermažar M, Serša I, Blagus T, Miklavčič D (2014) In situ monitoring of electric field distribution in mouse tumor during electroporation. Radiology 274(1):115–23. doi: 10.1148

    Google Scholar 

  • Kranjc M, Markelc B, Bajd F, Čemažar M, Serša I, Blagus T, Miklavčič D (2015) In situ monitoring of electric field distribution in mouse tumor during electroporation. Radiology 274:115–123

    Article  Google Scholar 

  • Lopez-Quintero SV, Datta A, Amaya R, Elwassif M, Bikson M, Tarbell JM (2010) DBS-relevant electric fields increase hydraulic conductivity of in vitro endothelial monolayers. J Neural Eng 7(1):16005. doi:10.1088/1741-2560/7/1/016005

    Article  Google Scholar 

  • Lozano AM, Hallett M (2013) Brain stimulation: handbook of clinical neurology (Series editors: Aminoff, Boller, Swaab), 3rd edn, vol 116. Elsevier: Newnes

    Google Scholar 

  • Markelc B, Sersa G, Cemazar M (2013) Differential mechanisms associated with vascular disrupting action of electrochemotherapy: intravital microscopy on the level of single normal and tumor blood vessels. PLoS One 8(3), e59557. doi:10.1371/journal.pone.0059557

    Article  Google Scholar 

  • Miklavcic D, Sersa G, Brecelj E, Gehl J, Soden D, Bianchi G, Ruggieri P, Rossi CR, Campana LG, Jarm T (2012) Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors. Med Biol Eng Comput 50(12):1213–1225. doi:10.1007/s11517-012-0991-8

    Article  Google Scholar 

  • Milojkovic Kerklaan B, van Tellingen O, Huitema AD, Beijnen JH, Boogerd W, Schellens JH, Brandsma D (2016) Strategies to target drugs to gliomas and CNS metastases of solid tumors. J Neurol 263(3):428–440. doi:10.1007/s00415-015-7919-9

    Article  Google Scholar 

  • Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood–brain barrier. Nat Med 19(12):1584–1596. doi:10.1038/nm.3407

    Article  Google Scholar 

  • Obermeier B, Verma A, Ransohoff RM (2016) The blood–brain barrier. Handb Clin Neurol 133:39–59. doi:10.1016/B978-0-444-63432-0.00003-7

    Article  Google Scholar 

  • Pucihar G, Krmelj J, Rebersek M, Napotnik TB, Miklavcic D (2011) Equivalent pulse parameters for electroporation. IEEE Trans Biomed Eng 58(11):3279–3288. doi:10.1109/TBME.2011.2167232

    Article  Google Scholar 

  • Sel D, Lebar AM, Miklavcic D (2007) Feasibility of employing model-based optimization of pulse amplitude and electrode distance for effective tumor electropermeabilization. IEEE Trans Biomed Eng 54(5):773–781. doi:10.1109/TBME.2006.889196

    Article  Google Scholar 

  • Sharabi S, Last D, Guez D, Daniels D, Hjouj MI, Salomon S, Maor E, Mardor Y (2014) Dynamic effects of point source electroporation on the rat brain tissue. Bioelectrochemistry 99:30–39. doi:10.1016/j.bioelechem.2014.06.001

    Article  Google Scholar 

  • Sharabi S, Kos B, Last D, Guez D, Daniels D, Harnof S, Mardor Y, Miklavcic D (2016) A statistical model describing combined irreversible electroporation and electroporation-induced blood–brain barrier disruption. Radiol oncol 50(1):28–38. doi:10.1515/raon-2016-0009

    Google Scholar 

  • van Tellingen O, Yetkin-Arik B, de Gooijer MC, Wesseling P, Wurdinger T, de Vries HE (2015) Overcoming the blood–brain tumor barrier for effective glioblastoma treatment. Drug resistance updat 19:1–12. doi:10.1016/j.drup.2015.02.002

    Article  Google Scholar 

  • Weaver JC, Smith KC, Esser AT, Son RS, Gowrishankar TR (2012) A brief overview of electroporation pulse strength-duration space: a region where additional intracellular effects are expected. Bioelectrochemistry 87:236–243. doi:10.1016/j.bioelechem.2012.02.007

    Article  Google Scholar 

  • Yarmush ML, Golberg A, Sersa G, Kotnik T, Miklavcic D (2014) Electroporation-based technologies for medicine: principles, applications, and challenges. Annu Rev Biomed Eng 16:295–320. doi:10.1146/annurev-bioeng-071813-104622

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Advanced Technology Center, Sheba Medical Center, Ramat-Gan, 52621, Israel

    Shirley Sharabi & Yael Mardor

  2. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel

    Shirley Sharabi & Yael Mardor

Authors
  1. Shirley Sharabi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yael Mardor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shirley Sharabi .

Editor information

Editors and Affiliations

  1. Faculty of Electrical Enginer, University of Ljubljana, Ljubljana, Slovenia

    Damijan Miklavcic

Section Editor information

  1. Department of Mechanical Engineering, University of California, 6124 Etcheverry Hall, Berkeley, CA 94720, Berkeley, California, USA

    Boris Rubinsky

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this entry

Cite this entry

Sharabi, S., Mardor, Y. (2016). Effect of Electroporation on Blood-Brain Barrier. In: Miklavcic, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-26779-1_168-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26779-1_168-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Online ISBN: 978-3-319-26779-1

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Societies and partnerships

Search

Navigation