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Neurotoxicity of Nanoparticles

Investigators from the National Center for Toxicological Research (NCTR) and Wright-Patterson Air Force Base have shown that 25-40 nanometer silver nanoparticles at concentrations of 15–50 micrograms per milliliter associate with the cells on the interior surface of the brain's micro-sized blood vessels (microvessel endothelial cells) and can induce:

significant cellular toxicity
alterations in cell form and structure
alterations in monolayer (layer of cells one cell thick) integrity
an increase in prostaglandin E2
tumor necrosis factor α
interleukin 1β

Primary rat-brain microvessel endothelial cells were used as an in vitro model of the blood brain barrier (BBB) to gain insight into the mechanisms involved in the nanoparticle-induced BBB dysfunction that has been reported. These studies indicate that silver nanoparticles produce an initial cascade of proinflammatory mediators that may contribute to increased BBB permeability, further brain inflammation, and neurotoxicity. Silver nanoparticles are widely used in engineering, manufacturing, and biomedicine. However, their impact on human health has not been adequately evaluated. A manuscript describing this research was recently accepted for publication (Toxicological Sciences, 2010).

For additional information, please contact Merle Paule, Ph.D., Director, Division of Neurotoxicology, FDA/NCTR.
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