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Review

Transendothelial Electrical Resistance Measurement across the Blood–Brain Barrier: A Critical Review of Methods

1
Institute of Biophysics, Biological Research Centre, 6726 Szeged, Hungary
2
Doctoral School of Biology, University of Szeged, 6720 Szeged, Hungary
3
Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark
4
In Vitro Metabolism Research, Division of Pharmacology and Drug Safety, Gedeon Richter Plc., 1103 Budapest, Hungary
5
Center for Health and Bioresources, Competence Unit Molecular Diagnostics, AIT—Austrian Institute of Technology GmbH, 1210 Vienna, Austria
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Current affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Academic Editor: Colin Dalton
Micromachines 2021, 12(6), 685; https://doi.org/10.3390/mi12060685
Received: 13 May 2021 / Revised: 4 June 2021 / Accepted: 8 June 2021 / Published: 11 June 2021
(This article belongs to the Special Issue Versatile Organ-on-a-Chip Devices)
The blood–brain barrier (BBB) represents the tightest endothelial barrier within the cardiovascular system characterized by very low ionic permeability. Our aim was to describe the setups, electrodes, and instruments to measure electrical resistance across brain microvessels and culture models of the BBB, as well as critically assess the influence of often neglected physical and technical parameters such as temperature, viscosity, current density generated by different electrode types, surface size, circumference, and porosity of the culture insert membrane. We demonstrate that these physical and technical parameters greatly influence the measurement of transendothelial electrical resistance/resistivity (TEER) across BBB culture models resulting in severalfold differences in TEER values of the same biological model, especially in the low-TEER range. We show that elevated culture medium viscosity significantly increases, while higher membrane porosity decreases TEER values. TEER data measured by chopstick electrodes can be threefold higher than values measured by chamber electrodes due to different electrode size and geometry, resulting in current distribution inhomogeneity. An additional shunt resistance at the circumference of culture inserts results in lower TEER values. A detailed description of setups and technical parameters is crucial for the correct interpretation and comparison of TEER values of BBB models. View Full-Text
Keywords: blood–brain barrier; cell culture insert; electrodes; endothelial cell; epithelial cell; impedance; lab-on-a-chip; transendothelial electrical resistance; viscosity blood–brain barrier; cell culture insert; electrodes; endothelial cell; epithelial cell; impedance; lab-on-a-chip; transendothelial electrical resistance; viscosity
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MDPI and ACS Style

Vigh, J.P.; Kincses, A.; Ozgür, B.; Walter, F.R.; Santa-Maria, A.R.; Valkai, S.; Vastag, M.; Neuhaus, W.; Brodin, B.; Dér, A.; Deli, M.A. Transendothelial Electrical Resistance Measurement across the Blood–Brain Barrier: A Critical Review of Methods. Micromachines 2021, 12, 685. https://doi.org/10.3390/mi12060685

AMA Style

Vigh JP, Kincses A, Ozgür B, Walter FR, Santa-Maria AR, Valkai S, Vastag M, Neuhaus W, Brodin B, Dér A, Deli MA. Transendothelial Electrical Resistance Measurement across the Blood–Brain Barrier: A Critical Review of Methods. Micromachines. 2021; 12(6):685. https://doi.org/10.3390/mi12060685

Chicago/Turabian Style

Vigh, Judit P., András Kincses, Burak Ozgür, Fruzsina R. Walter, Ana Raquel Santa-Maria, Sándor Valkai, Mónika Vastag, Winfried Neuhaus, Birger Brodin, András Dér, and Mária A. Deli. 2021. "Transendothelial Electrical Resistance Measurement across the Blood–Brain Barrier: A Critical Review of Methods" Micromachines 12, no. 6: 685. https://doi.org/10.3390/mi12060685

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