An in vitro blood-brain barrier model for high throughput (HTS) toxicological screening

Abstract : There is a growing interest to use in vitro BBB cell assays in early safety assessment of compounds. By modifying a well-validated coculture model of brain capillary endothelial and glial cells, developed by Dehouck et al. [Dehouck, M.P., Meresse, S., Delorme, P., Fruchart, J.C., Cecchelli, R., 1990. An easier, reproducible, and mass-production method to study the blood-brain barrier in vitro. Journal of Neurochemistry 54 (5), 1798–1801], it has been possible to develop a new in vitro BBB system suitable for high throughput screening (HTS). In addition, this new procedure substantially reduces the use of experimental animals and considerably facilitates the process of obtaining a functional in vitro BBB model. The model is ready to use after only 4 days of culture and then shows the typical expression and localization of tight junction proteins. The function of the P-glycoprotein and the transcriptional expression of other efflux transporters such as MRP 1, 4 and 5 have been demonstrated. In addition, the model produces a good in vitro/in vivo correlation for 10 compounds (R2 = 0.81). Furthermore, studies were undertaken within the European ACuteTox consortium with the objective to assess BBB toxicity and make risk assessments of potentially toxic compounds according to their predicted ability to reach the CNS compartment. These investigations demonstrated that the results produced in the HTS BBB model were similar to the standard co-culture model.
Type de document :
Article dans une revue
Toxicology in Vitro, Elsevier, 2008, 22, p. 799-811
Liste complète des métadonnées

https://hal-univ-artois.archives-ouvertes.fr/hal-00527560
Contributeur : Wilfried Déplanques <>
Soumis le : mardi 19 octobre 2010 - 15:52:31
Dernière modification le : mercredi 20 octobre 2010 - 10:16:51

Identifiants

  • HAL Id : hal-00527560, version 1

Collections

Citation

Maxime Culot, Stefan Lundquist, Dorothée Vanuxeem, Stéphane Nion, Christophe Landry, et al.. An in vitro blood-brain barrier model for high throughput (HTS) toxicological screening. Toxicology in Vitro, Elsevier, 2008, 22, p. 799-811. 〈hal-00527560〉

Partager

Métriques

Consultations de la notice

117