In vitro models of the blood-brain barrier.

In this literature review 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.

[1]  S. Heales,et al.  Decreased endothelial cell glutathione and increased sensitivity to oxidative stress in an in vitro blood–brain barrier model system , 1998, Brain Research.

[2]  J. Howl,et al.  Critical Evaluation of ECV304 as a Human Endothelial Cell Model Defined by Genetic Analysis and Functional Responses: A Comparison with the Human Bladder Cancer Derived Epithelial Cell Line T24/83 , 2000, Laboratory Investigation.

[3]  L. Fenart,et al.  In vitro model for evaluating drug transport across the blood-brain barrier. , 1999, Advanced drug delivery reviews.

[4]  S. Kuchler-Bopp,et al.  Astrocytes induce several blood-brain barrier properties in non-neural endothelial cells. , 1999, Neuroreport.

[5]  R. Janzer,et al.  Astrocytes induce blood–brain barrier properties in endothelial cells , 1987, Nature.

[6]  S. Wold,et al.  The Collinearity Problem in Linear Regression. The Partial Least Squares (PLS) Approach to Generalized Inverses , 1984 .

[7]  M. Wiley,et al.  Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail--chick transplantation chimeras. , 1981, Developmental biology.

[8]  W. Pardridge 6 – Blood-Brain Barrier Transport Mechanisms , 1997 .

[9]  R. Hurst,et al.  Properties of an immortalised vascular endothelial/glioma cell co‐culture model of the blood‐brain barrier , 1996, Journal of Cellular Physiology.

[10]  B. Veronesi Characterization of the MDCK cell line for screening neurotoxicants. , 1996, Neurotoxicology.

[11]  F. Lombardo,et al.  Computation of brain-blood partitioning of organic solutes via free energy calculations. , 1996, Journal of medicinal chemistry.

[12]  Michael Balls,et al.  The Role of Prevalidation in the Development, Validation and Acceptance of Alternative Methods , 1995 .

[13]  K. Luthman,et al.  Caco-2 monolayers in experimental and theoretical predictions of drug transport , 1996 .

[14]  K D Pettigrew,et al.  Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. , 1978, The American journal of physiology.

[15]  U. Ungerstedt,et al.  A comparison between three methods for estimation of extracellular concentrations of exogenous and endogenous compounds by microdialysis. , 1991, Journal of pharmacological methods.

[16]  H. Lennernäs,et al.  Comparison between active and passive drug transport in human intestinal epithelial (Caco-2) cells in vitro and human jejunum in vivo , 1996 .

[17]  M. Dehouck,et al.  Drug transport to the brain: comparison between in vitro and in vivo models of the blood-brain barrier , 1995 .