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.