ATLA::Alternatives to Laboratory Animals

Volume 31, Number 3

Refining in vitro neurotoxicity testing -- the development of blood-brain barrier models.

Hanna TÄHti1, Heidi Nevala2 and Tarja Toimela1

1Cell Research Centre, Medical School, University of Tampere, 33014 Tampere, Finland; 2Department of Biological and Environmental Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland

SUMMARY

The purpose of this paper is to review the current state of development of advanced in vitro bloodbrain 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 enclothelial cells in culture lose their barrier characteristics. Therefore, when developing in vitro BBB 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 vivo functions of the BBB in an effective way. With a BBB model, kinetic factors can be added into the in vitro batteries used for evaluating the neurotoxic potential of chemicals. The in vitro BBB model also represents a useful tool for the in vitro prediction 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 enclothelial 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.

Keywords: blood-brain barrier, co-culture techniques, in vitro