Aluminum effects on brain microvessel endothelial cell monolayer permeability

Abstract

The permeability of primary cultures of brain microvessel endothelial cell (BMEC) monolayers has been shown to be sensitive to micromolar concentrations of aluminum. Aluminum increased BMEC permeability to a biomembrane impermeant molecule, fluorescein sodium, in a concentration-dependent manner with maximal effects observed after a 5 min preincubation. Aluminum attenuated BMEC pinocytosis as quantitated by the uptake of Lucifer yellow, a fluorescent marker for fluid-phase pinocytosis. Following labeling BMEC membranes with either diphenylhexatriene or trimethylammonium diphenylhexatriene, fluorescence anisotropy measurements showed that aluminum has no effect on membrane lipid order neither at the core of BMEC membranes nor near the surface of the BMEC membrane. The absence of aluminum-induced increases in BMEC pinocytosis, the absence of aluminum effects on BMEC lipid order, and the rapid onset of concetration-dependent increases in BMEC monolayer permeability suggests the potential site of aluminum-induced alterations of BBB permeability may originate at the luminal BMEC surface. Results confirm and support in vivo findings of aluminum-induced increases in blood-brain barrier (BBB) permeability to peptides and non-peptides. We conclude that primary cultures of BMEC monolayers provide an appropriate in vitro model for molecular/cellular level elucidation of mechanisms modulating BBB permeability to blood-borne factors.