Butyric acid mediated induction of enhanced transendothelial resistance inan in vitro model blood-brain barrier system

Previously we reported that the co-culture of non-brain vascular endothelia l cells with glioma cells leads to the induction of a more differentiated e ndothelial cell phenotype which exhibits important properties of the blood- brain barrier (BBB). Recognising the potential for improving the model barr ier system with agents known to modify the growth and differentiation of ce lls in culture we examined the effects of four differentiating agents (buty ric acid, dexamethasone, retinoic acid, and dimethyl sulfoxide) on barrier function. Of these agents only butyric acid and dexamethasone resulted in a n enhancement (depending on the dose used) of transendothelial electrical r esistance (barrier function). The greatest effect was observed with butyric acid in a dose-dependent manner and was slow in onset and only occurred in the endothelial/glial cell co-cultures. These data indicate that butyric a cid may be a beneficial agent in optimising conditions necessary for induct ion of BBB properties in in vitro barrier systems. (C) 1999 Elsevier Scienc e Ltd. All rights reserved.