ATLA::Alternatives to Laboratory Animals

Volume 26, Number 6

In vitro models of the blood-brain barrier.

ATLA 26, 821-847, November/December 1998

Per Garberg

Preformulation Sciences, Biopharmaceutics, Pharmacia & Upjohn AB, 112 87 Stockholm, Sweden

SUMMARY

In this literature renew on in vitro models of the blood-brain barrier (BBB), it is concluded that there is a need to identify a unified in vitro model for the BBB. The best evaluated model at present is based on the use of primary cultures of bovine brain endothelial cells. Primary cell cultures are usually shown to retain several BBB characteristics, but are time-consuming and difficult to establish. To make a unified in vitro model for the BBB more generally available, it is strongly suggested that such a model should be based on the use of an established cell line. To identify the best in vitro model, an evaluation of the most promising immortalised BBB-derived endothelial cell lines, as well as other established cell lines presently used as BBB models, is highly recommended. An evaluation of possible species variation is also important in order to establish the most relevant species to be used. Furthermore, it is also suggested that the specific properties of in vitro BBB models, as compared to models for the "intestinal barrier", for example, should be evaluated. Finally, it is recommended that an evaluation of available computer models is performed, to further improve early predictions for drug candidates with regard to BBB permeability.

Keywords: Blood-brain barrier, in vitro modelling, permeability