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Differential opening of the brain endothelial barrier following neutralization of the endothelial luminal anionic charge in vitro.

This study was undertaken to determine the effect of neutralization of brain endothelial cell luminal membrane anionic charge on endothelial permeability properties. Mouse brain microvessel endothelial cells were grown to confluence on a nitrocellulose filter. The permeability of the endothelium to Evan's blue dye (EBD) (molecular weight 960) and fluoresceinated dextran (FITC-D) (molecular weight 20,000), both polar molecules, was assessed before and after the exposure of the endothelium to cationic ferritin (CF) or native ferritin (NF). The use of CF resulted in a significant increase in permeability of the endothelium to EBD compared to NF. This result indicates that ablation of endothelial surface anionic charge enhances endothelial transport of a small, polar-charged molecule. Cationic ferritin did not increase the permeability of FITC-D compared to NF. This negative result is not surprising because FITC-D differs from EBD in terms of charge and solubility as well as in size. The electrical resistance of the endothelial cell layer after the application of CF was unchanged from baseline values suggesting a transcellular rather than a paracellular route of the EBD leakage.