The studies was to determine what role the microvessel endothelial cells that comprise the blood-brain barrier (BBB) have in brain inflammation and neurotoxicity associated with metallic nanoparticles (NPs) like silver (Ag), gold (Au) and copper (Cu).A primary culture of rat brain microvessel endothelial cells (rMVEC) was isolated for an in vitro model of the BBB. Confluent rMVEC monolayers were treated with various sized Ag or Au or Cu NPs. The cellular accumulation of the NPs was determined spectrophotometrically and cytotoxicity was evaluated by XTT. The extracellular concentrations of proinflammatory mediators (IL-1B, IL-2, TNFa and PGE2) were evaluated by ELISA.  The magnitude of cellular accumulation was size dependent and similar for all NPs. The cytotoxicity of rMVEC following 24-hrs of exposure to Ag-NPs (LD50; below 700 ng/ml (25 nm) and 10ug/ml (40 and 80 nm)) was significantly increased, when compared to Au-NPs where as Cu-NPs LD50 was approximately 12.5 ug/ml for both sized. Au-NPs above 3 nm in size showed no significant cytotoxic effects. PGE2 release following Ag and Cu NPs exposure was significantly increased when compared to control. The basal levels of TNF and IL-1B were significantly increased following Ag or Cu NPs, but not with Au-NPs. These data suggest that the brain microvessel endothelial cells may play a significant role in the neurotoxicity associated with Ag, Au or Cu NPs.

Engineered metallic nanoparticles and blood-brain-barrier

243rd National Meeting (2012)

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