Nanosized titanium dioxide enhanced inflammatory responses in the septic brain of mouse

Nanosized titanium dioxide (TiO2) is used widely in various everyday products and can be applied to the medical field for diagnostic or therapeutic tools. However, its neurobiological responses have not been defined completely in the brain. To evaluate the acute inflammatory response to TiO2 particles of two different sizes in normal and septic brains, male C57BL/6 mice were given intraperitoneal injections of fine (<1 μm) or ultrafine (21 nm) TiO2, 30 min after vehicle or lipopolysaccaride (LPS). In the normal brain, neither fine nor ultrafine TiO2 induced inflammation. However, in the brains of LPS-exposed mice, ultrafine TiO2 significantly elevated proinflammatory cytokine interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mRNAs, and IL-1β protein levels. Also ultrafine TiO2 increased the levels of reactive oxygen species and activated microglia 24 h after LPS challenge. In BV2 microglial cells stimulated with LPS, ultrafine TiO2 enhanced TNF-α production and augmented nuclear factor-kB binding activity. These findings suggest that nanosized TiO2 promotes an exaggerated neuroinflammatory responses by enhancing microglial activation in the pre-inflamed brain, in part.