William R Pritchard Veterinary Medical Teaching Hospital, University of California, Davis, Davis, California, USA.
Center for Health and the Environment, University of California, Davis, Davis, California, USA.
Toxicol Pathol. 2022 Aug;50(6):763-775. doi: 10.1177/01926233221107607. Epub 2022 Jun 29.
Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO may have translocated to the central nervous system via intra-neuronal pathways.
工程化的银纳米粒子(AgNPs),包括硅酸银纳米粒子(Ag-SiO NPs),被广泛应用于医学和消费领域。研究发现,吸入的 AgNPs 经吸入和鼻腔内滴注后会转移到嗅球(OB)。然而,Ag-SiO NPs 的生物学效应及其潜在的鼻脑转运尚未得到评估。本研究评估了吸入的 Ag-SiO NPs 是否会引起 OB 中的小胶质细胞激活。成年 Sprague-Dawley 大鼠以 1mg/ml 的浓度吸入雾化的 Ag-SiO NPs 6 小时。在暴露后第 0、1、7 和 21 天,大鼠进行安乐死并采集 OB。使用抗离子钙结合接头分子 1 和血红素加氧酶-1 作为小胶质细胞激活和氧化应激的标志物,对 OB 组织进行免疫组织化学染色。气溶胶特性分析表明,Ag-SiO NPs 被充分气溶胶化,在鼻腔和嗅上皮中具有中度团聚和高效沉积。结果表明,急性吸入 Ag-SiO NPs 会引起 OB 中短暂且不同的小胶质细胞激活,而不会引起小胶质细胞募集或氧化应激。OB 中延迟且不同的小胶质细胞激活模式表明,吸入的 Ag-SiO 可能通过神经元内途径转移到中枢神经系统。