Refining In VitroNeurotoxicity Testing — The Development of Blood–Brain Barrier Models

Autor: Tähti, Hanna, Nevala, Heidi, Toimela, Tarja
Zdroj: Alternatives to Laboratory Animals; May 2003, Vol. 31 Issue: 3 p273-276, 4p
Abstrakt: The purpose of this paper is to review the current state of development of advanced in vitroblood–brain barrier (BBB) models. The BBB is a special capillary bed that separates the blood from the central nervous system (CNS) parenchyma. Astrocytes maintain the integrity of the BBB, and, without astrocytic contacts, isolated brain capillary endothelial cells in culture lose their barrier characteristics. Therefore, when developing in vitroBBB models, it is important to add astrocytic factors into the culture system. Recently, novel filter techniques and co-culture methods have made it possible to develop models which resemble the in vivofunctions of the BBB in an effective way. With a BBB model, kinetic factors can be added into the in vitrobatteries used for evaluating the neurotoxic potential of chemicals. The in vitroBBB model also represents a useful tool for the in vitroprediction of the BBB permeability of drugs, and offers the possibility to scan a large number of drugs for their potential to enter the CNS. Cultured monolayers of brain endothelial cell lines or selected epithelial cell lines, combined with astrocyte and neuron cultures, form a novel three-dimensional technique for the screening of neurotoxic compounds.
Databáze: Supplemental Index