TY - JOUR

T1 - Transendothelial electrical resistance measurement across the blood–brain barrier

T2 - A critical review of methods

AU - Vigh, Judit P.

AU - Kincses, András

AU - Ozgür, Burak

AU - Walter, Fruzsina R.

AU - Santa-Maria, Ana Raquel

AU - Valkai, Sándor

AU - Vastag, Mónika

AU - Neuhaus, Winfried

AU - Brodin, Birger

AU - Dér, András

AU - Deli, Mária A.

N1 - Funding Information: This research was funded by the National Research, Development, and Innovation Office of Hungary grant numbers OTKA NNE 129617 (as part of the M-Era.NET2 nanoPD project to M.A.D.) and PD-128480 (to F.R.W.), by the Lundbeck Foundation, grant no. R155-2013-14113 (?Research Initiative on Brain Barriers and Drug Delivery?, to B.B.) and by the European Union?s Horizon 2020 research and innovation program Innovative Medicines Initiative (IMI), grant number 807015 (Innovative Medicines Initiative 2 Joint Undertaking, to B.B.). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - The blood–brain barrier (BBB) represents the tightest endothelial barrier within the cardio-vascular 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.

AB - The blood–brain barrier (BBB) represents the tightest endothelial barrier within the cardio-vascular 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.

KW - Blood–brain barrier

KW - Cell culture insert

KW - Electrodes

KW - Endothelial cell

KW - Epithelial cell

KW - Impedance

KW - Lab-on-a-chip

KW - Transendothelial electrical resistance

KW - Viscosity

U2 - 10.3390/mi12060685

DO - 10.3390/mi12060685

M3 - Review

C2 - 34208338

AN - SCOPUS:85108703107

VL - 12

JO - Micromachines

JF - Micromachines

SN - 2072-666X

IS - 6

M1 - 685

ER -