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暴露于吸入性气溶胶后不同理化形态铀的经鼻向脑输送评价。

Evaluation of the Nose-to-Brain Transport of Different Physicochemical Forms of Uranium after Exposure Inhalation of a Aerosol in the Rat.

机构信息

Institut de Radioprotection et de Sûreté Nucléaire, Pôle Santé Environnement, Service de recherche sur les effets biologiques et sanitaires des rayonnements ionisants, Laboratoire de Radiotoxicologie et Radiobiologie Expérimentale, Fontenay aux Roses, France.

Institut de Radioprotection et de Sûreté Nucléaire, Pôle Santé Environnement, Service de recherche sur les effets biologiques et sanitaires des rayonnements ionisants, Laboratoire de Recherche en Radiochimie, Spéciation et Imagerie, Fontenay aux Roses, France.

出版信息

Environ Health Perspect. 2019 Sep;127(9):97010. doi: 10.1289/EHP4927. Epub 2019 Sep 30.

Abstract

BACKGROUND

Health-risk issues are raised concerning inhalation of particulate pollutants that are thought to have potential hazardous effects on the central nervous system. The brain is presented as a direct target of particulate matter (PM) exposure because of the nose-to-brain pathway involvement. The main cause of contamination in nuclear occupational activities is related to exposure to aerosols containing radionuclides, particularly uranium dust. It has been previously demonstrated that instilled solubilized uranium in the rat nasal cavity is conveyed to the brain via the olfactory nerve.

OBJECTIVE

The aim of this study was to analyze the anatomical localization of uranium compounds in the olfactory system after exposure to a polydisperse aerosol of uranium tetraoxide () particles.

METHODS

The olfactory neuroepithelium (OE) and selected brain structures-olfactory bulbs (OB), frontal cortex (FC), hippocampus (HIP), cerebellum (Cer), and brainstem (BS)-were microdissected 4 h after aerosol inhalation a nose-only system in adult rats. Tissues were subjected to complementary analytical techniques.

RESULTS

Uranium concentrations measured by inductively coupled plasma mass spectrometry (ICP-MS) were significantly higher in all brain structures from exposed animals compared with their respective controls. We observed that cerebral uranium concentrations followed an anteroposterior gradient with typical accumulation in the OB, characteristic of a direct olfactory transfer of inhaled compounds. Secondary ion mass spectrometry (SIMS) microscopy and transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy (TEM-EDX) were used in order to track elemental uranium in the olfactory epithelium. Elemental uranium was detected in precise anatomical regions: olfactory neuron dendrites, paracellular junctions of neuroepithelial cells, and olfactory nerve tracts (around axons and endoneural spaces).

CONCLUSION

These neuroanatomical observations in a rat model are consistent with the transport of elemental uranium in different physicochemical forms (solubilized, nanoparticles) along olfactory nerve bundles after inhalation of microparticles. This work contributes to knowledge of the mechanistic actions of particulate pollutants on the brain. https://doi.org/10.1289/EHP4927.

摘要

背景

吸入被认为对中枢神经系统有潜在危害的颗粒污染物会引发健康风险问题。由于涉及鼻至脑途径,大脑被认为是颗粒物质(PM)暴露的直接靶标。核职业活动中的主要污染原因与暴露于含有放射性核素的气溶胶有关,特别是铀尘。先前已经证明,将可溶解的铀注入大鼠鼻腔后,会通过嗅神经输送到大脑。

目的

本研究的目的是分析吸入四氧化铀()多分散气溶胶后,铀化合物在嗅觉系统中的解剖定位。

方法

在成年大鼠经鼻吸入系统中吸入气溶胶 4 小时后,通过微切割嗅神经上皮(OE)和选定的脑结构-嗅球(OB)、额皮质(FC)、海马(HIP)、小脑(Cer)和脑干(BS),分析其解剖定位。对组织进行了补充分析技术。

结果

电感耦合等离子体质谱(ICP-MS)测量的铀浓度在暴露动物的所有脑结构中均明显高于各自的对照。我们观察到,大脑中的铀浓度呈前后梯度分布,在 OB 中典型地积聚,这表明吸入化合物的直接嗅觉转移。二次离子质谱(SIMS)显微镜和与能量色散 X 射线光谱(TEM-EDX)相结合的透射电子显微镜用于在嗅上皮中追踪元素铀。在嗅神经元树突、神经上皮细胞的旁细胞连接和嗅神经束(在轴突和神经内膜空间周围)中检测到元素铀。

结论

在大鼠模型中的这些神经解剖学观察结果与吸入微颗粒后,不同物理化学形式(可溶解、纳米颗粒)的元素铀沿着嗅神经束的运输一致。这项工作有助于了解颗粒污染物对大脑的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d28/6791583/fa99e7a97863/ehp-127-097010-g0001.jpg

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