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. 2022 Mar 1;12:3384. doi: 10.1038/s41598-022-07247-8

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Penetration of the selected HR compounds through in vitro BBB model membrane: (A) Schematic representation of a triple-coculture model of the BBB, which consists of astrocytes, pericytes and epithelial cells cultured on 24-well transwell membranes with 3 μm pores. Trans-endothelial electric resistance (TEER) was measured using a EVOM² meter with a STX3 electrode (World Precision Instruments). (B) Measurements of the electric resistance of inserts used for specific compounds (Ω); Difference between resistance of the insert with established BBB versus empty insert (Ω_BBB − Ω_insert); and trans-endothelial electric resistance (TEER; Ω_BBB − Ω_insert/cm²). * TEER coefficient = TEER_compound/TEER_caffeine. TEER coefficients were used to normalize BBB permeability (P) values to compensate for differences in TEER values between inserts selected for each compound. (C) Differences in BBB permeability (P) calculated using P = V_A·C_A/(t·S·C_L) eqution⁷⁰ and normalized by TEER coefficient. Data represent average values from 2 independent experiments in triplicates (n = 6) with standard deviation SD. *Indicates values significantly different from fenofibrate (internal negative control).