Department of Pharmacology, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Neuroscience. 2010 Jan 20;165(2):445-54. doi: 10.1016/j.neuroscience.2009.10.057.
Nanosized titanium dioxide (TiO(2)) 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 TiO(2) particles of two different sizes in normal and septic brains, male C57BL/6 mice were given intraperitoneal injections of fine (<1 microm) or ultrafine (21 nm) TiO(2), 30 min after vehicle or lipopolysaccaride (LPS). In the normal brain, neither fine nor ultrafine TiO(2) induced inflammation. However, in the brains of LPS-exposed mice, ultrafine TiO(2) significantly elevated proinflammatory cytokine interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mRNAs, and IL-1beta protein levels. Also ultrafine TiO(2) increased the levels of reactive oxygen species and activated microglia 24 h after LPS challenge. In BV2 microglial cells stimulated with LPS, ultrafine TiO(2) enhanced TNF-alpha production and augmented nuclear factor-kB binding activity. These findings suggest that nanosized TiO(2) promotes an exaggerated neuroinflammatory responses by enhancing microglial activation in the pre-inflamed brain, in part.
纳米级二氧化钛 (TiO(2)) 广泛应用于各种日常产品，并可应用于医学领域的诊断或治疗工具。然而，其在大脑中的神经生物学反应尚未完全确定。为了评估两种不同尺寸的 TiO(2) 纳米颗粒在正常和脓毒症大脑中的急性炎症反应，雄性 C57BL/6 小鼠在给予 vehicle 或脂多糖 (LPS) 30 分钟后，经腹腔注射细 (<1 微米) 或超细 (21nm) TiO(2)。在正常大脑中，细 TiO(2) 和超细 TiO(2) 均未引起炎症。然而，在 LPS 暴露的小鼠大脑中，超细 TiO(2) 显著增加了促炎细胞因子白细胞介素-1β (IL-1β) 和肿瘤坏死因子-α (TNF-α) mRNA 的水平，以及 IL-1β 蛋白水平。此外，超细 TiO(2) 在 LPS 攻击后 24 小时增加了活性氧和激活的小胶质细胞的水平。在 LPS 刺激的 BV2 小胶质细胞中，超细 TiO(2) 增强了 TNF-α 的产生，并增强了核因子-kB 结合活性。这些发现表明，纳米级 TiO(2) 通过增强前炎症大脑中小胶质细胞的激活，促进了神经炎症反应的过度发生。
