Gilda Shayan - Murine in vitro model of the blood-brain barrier for evaluating drug transport.

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    Eur J Pharm Sci. 2011 Jan 18;42(1-2):148-55. Epub 2010 Nov   13.


  In vitro blood-brain barrier (BBB) models help predict brain   uptake of potential central nervous system drug candidates.   Current in vitro models are composed of brain microvascular   endothelial cells (BMEC) that are isolated from rat, bovine, or   porcine. However, most in vivo studies on drug transport through   the BBB are performed in small laboratory animals, specially   mouse and thus murine in vitro BBB models serve as better   surrogates to correlate with these studies. Here we describe the   functional characterization of a reproducible in vitro model   composed of murine BMEC co-cultured with rat primary astrocytes   in the presence of biochemical inducing agents. The co-cultures   presented high TEER and low sodium fluorescein permeability.   Expression of specific BBB tight junction proteins (occludin,   claudin-5, ZO-1) and the functionality of transporters (Pgp,   GLUT1) were detected by immunocytochemistry and Western blotting.   These results indicated a 2.5-fold increase in the expression   levels of these proteins in the presence of astrocytes. In   addition, a high correlation coefficient (0.98) was obtained   between the permeability of a series of hydrophobic and   hydrophilic drugs and their corresponding in vivo values. These   results together establish the utility of this murine model for   future drug transport, pathological, and pharmacological   characterizations of the BBB.

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