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- W2978403702 abstract "Vol. 127, No. 9 ResearchOpen AccessEvaluation of the Nose-to-Brain Transport of Different Physicochemical Forms of Uranium after Exposure via Inhalation of a UO4 Aerosol in the Rat Chrystelle Ibanez, David Suhard, Christelle Elie, Teni Ebrahimian, Philippe Lestaevel, Audrey Roynette, Bernadette Dhieux-Lestaevel, François Gensdarmes, Karine Tack, and Christine Tessier Chrystelle Ibanez 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 Search for more papers by this author , David Suhard 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 Search for more papers by this author , Christelle Elie Address correspondence to Dr. Chrystelle Ibanez, IRSN/PSE-SANTE/SESANE, LRTOX, BP17, 92262 Fontenay aux Roses Cedex, France. Telephone: +33 (0) 1 58 35 82 84. Fax: +33 (0) 1 58 35 84 67. Email: E-mail Address: [email protected] 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 Search for more papers by this author , Teni Ebrahimian 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 Search for more papers by this author , Philippe Lestaevel 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 Search for more papers by this author , Audrey Roynette Institut de Radioprotection et de Sûreté Nucléaire, Pôle de Sûreté des Installations et des Systèmes Nucléaire, Service du Confinement et de l’Aérodispersion des Polluants, Laboratoire de Physique et de Métrologie des Aérosols, Gif-sur-Yvette, France Search for more papers by this author , Bernadette Dhieux-Lestaevel Institut de Radioprotection et de Sûreté Nucléaire, Pôle de Sûreté des Installations et des Systèmes Nucléaire, Service du Confinement et de l’Aérodispersion des Polluants, Laboratoire de Physique et de Métrologie des Aérosols, Gif-sur-Yvette, France Search for more papers by this author , François Gensdarmes Institut de Radioprotection et de Sûreté Nucléaire, Pôle de Sûreté des Installations et des Systèmes Nucléaire, Service du Confinement et de l’Aérodispersion des Polluants, Laboratoire de Physique et de Métrologie des Aérosols, Gif-sur-Yvette, France Search for more papers by this author , Karine Tack 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 Search for more papers by this author , and Christine Tessier Institut de Radioprotection et de Sûreté Nucléaire, Fontenay aux Roses, France Search for more papers by this author Published:30 September 2019CID: 097010https://doi.org/10.1289/EHP4927Cited by:5AboutSectionsPDF ToolsDownload CitationsTrack CitationsCopy LTI LinkHTMLAbstractPDF ShareShare onFacebookTwitterLinked InRedditEmail AbstractBackground: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 in vivo exposure to a polydisperse aerosol of uranium tetraoxide (UO4) 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 via 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 situ 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 UO4 microparticles. This work contributes to knowledge of the mechanistic actions of particulate pollutants on the brain. https://doi.org/10.1289/EHP4927IntroductionThe association between exposure to particulate pollutants via inhalation and the increased risk of deleterious effects on the central nervous system is an emerging issue. Numerous experimental and epidemiological studies have focused on the biological effects of particulate matter (PM) on the respiratory and cardiovascular systems, and there is now growing evidence that the brain could be a direct target after exposure via inhalation (Heusinkveld et al. 2016; Oberdörster et al. 2009). The potential deleterious effect of PM inhalation is relevant to the global population, in part because of the many pathways for exposure and, PM, for instance, is widely mentioned in relationship to environmental exposure due to traffic-related air pollution.The literature (including in vitro, in vivo animal, and epidemiological studies) describes solid observations of the negative impact of PM on neurological functions (Lucchini et al. 2012). Several studies have focused on the biological effects on the brain of air pollution in large urban areas. An epidemiological study has suggested that long-term exposure to traffic-related air pollution could be an important risk factor for vascular dementia and Alzheimer’s disease in a major city in northern Sweden (Oudin et al. 2016). Studies of selected canine subjects [7 dogs from Mexico City compared with 14 dogs from another city with lower air pollution (Calderón-Garcidueñas et al. 2008)] and postmortem analyses in children [9 children from Mexico City compared with 6 children from another city with lower air pollution; (Calderón-Garcidueñas et al. 2016)] point to a trigger of a neuroinflammation process in the brain of exposed dogs and humans (Block and Calderón-Garcidueñas 2009). Postmortem analyses of Mexican children exposed to high air pollution showed white matter lesions in the prefrontal cortex (Calderón-Garcidueñas et al. 2016). These observations were extended last year by experimental rodent studies suggesting direct effects of PM on the neuroinflammation process, in particular, prenatal exposure to diesel exhaust (DE) particles in microglial cell activation in male mice (Bolton et al. 2017), an effect of ammonium sulfate exposure on neuronal maturation in adult male mice (Cheng et al. 2017), and exposure to nanoscale PM in neuronal atrophy in young female mice (Woodward et al. 2017). Neuroinflammation appears to be the first trigger of the central effects of PM (Jayaraj et al. 2017).Health risks associated with exposure via particle inhalation may also be encountered in specific occupational activities. In nuclear facilities, contaminations are mainly caused by airborne PM, i.e., particularly aerosols in mines and during nuclear fuel cycle operations, and nuclear dismantling represents a potential hazard for exposed workers (Anderson et al. 2016; Samson et al. 2016). We believe that the latter operations will become more and more frequent in the future and are the cause of radioactive particle resuspension or direct emission (Chae et al. 2019; Peillon et al. 2017). Aerosols contain particles ranging in size (micrometric to nanometric) and chemical composition, including dust containing uranium particles [mainly uranium oxide particles].The involvement of the nose-to-brain pathway is suggested by Lucchini et al. (2012) and Oberdörster et al. (2004), and the latter refers to cerebral effects of inhaled ultrafine particles in rat models.In 2016, Maher et al. illustrated the extent to which the olfactory system is a strong link between the external environment and the central nervous system, as they observed magnetite particles of exogenous origin in the human brain (Maher et al. 2016). The literature also suggests the involvement of the olfactory pathway for other metals: mercury (Henriksson and Tjalve 1998), cobalt (Persson et al. 2003), and cadmium (Bondier et al. 2008) after nasal instillation or nebulization, and for ultrafine manganese oxide particles after inhalation (Elder et al. 2006).With regard to uranium, pilot studies strongly suggest that it can be transferred to the brain in rats exposed to repeated depleted uranium oxide aerosol inhalation (uranium oxide powder is depleted in U235 as compared with natural uranium). In an inductively coupled plasma mass spectrometry (ICP-MS) analysis, Monleau et al. (2005) revealed that elemental uranium accumulated in the olfactory bulbs (OB) of male rats, even though the final physicochemical form was not studied (Monleau et al. 2005). Subsequently, Tournier et al. (2009) confirmed a uranium anteroposterior gradient in the brains of male rats after inhalation, and proposed a direct role of the olfactory neurons in its transfer (Tournier et al. 2009). Our recent study has strengthened this hypothesis. We demonstrated, using secondary ion mass spectrometry (SIMS) microscopy, uranium transport along olfactory nerve bundles of male rats and delivery to the brain via the cerebrospinal fluid after intranasal instillation of depleted uranium (Ibanez et al. 2014).The concern in terms of potential neurotoxicity of uranium after exposure via aerosol inhalation is linked to its dual toxicity: chemical, as it is a heavy metal, and radiotoxicity, due to its radioactivity. It will also be important to consider the influence of the physicochemical changes of uranium particles on the subsequent biological effects and mechanisms of transport to the brain (solubilized compounds, nanoparticles, and ion forms). For instance, different physicochemical forms of cerium dioxide nanoparticles induce differential toxicity responses in rodents after inhalation (Dekkers et al. 2018). In the inhalation mode of exposure, one study demonstrated that uranium-exposed male rats exhibited poorer performance in spatial working memory tests than did control rats (Monleau et al. 2005). These experiments raise concerns in terms of cognitive impairments provoked by inhalation of aerosolized uranium particles. In terms of radioprotection, biological contamination follow-up is based on biokinetic models that have been developed to predict uranium distribution in the main body compartments, particularly after contamination by inhalation (ICRP 1994). However, these models do not take into account the potential existence of direct transfer of uranium to the brain via the olfactory pathway (ICRP 1994).We thus decided to continue our previous investigations using a model of inhalation exposure to uranium tetraoxide (UO4) particles. The aim of this study was to provide robust anatomical evidence of the localization of elemental uranium in the olfactory system after exposure of adult male rats to UO4 aerosol via nose-only inhalation. These experiments complement the observations made using the intranasal administration model with an aqueous solution containing solubilized uranium (Ibanez et al. 2014). A precise definition of elemental uranium distribution after exposure to the uranium particulate form will provide evidence for the existence of a specific uranium olfactory route.Adult male rats were exposed to a polydisperse aerosol of UO4 using nose-only inhalation chambers. Elemental uranium concentrations resulting from these exposures were measured by ICP-MS in different brain structures along the anteroposterior axis of the brain: olfactory bulb (OB), frontal cortex (FC), hippocampus (HIP), cerebellum (Cer), and brainstem (BS). In order to detect in situ localization of solubilized and particulate forms of uranium in the olfactory neuroepithelium (OE), we used two different high-resolution microscopy techniques: SIMS microscopy, a very sensitive surface analysis technique able to map uranium distribution in tissue sections, and transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy (TEM-EDX), which provides detection at a nanoscale dimension and characterizes chemical elements.MethodsAnimalsAdult male Sprague-Dawley rats (12 wk old) from Charles River Laboratories were used for all experiments. Animals were housed in the IRSN (Institut de Radioprotection et de Sûreté Nucléaire) animal facilities accredited by the French Ministry of Agriculture. Food and water were provided ad libitum (lights on: 0800 to 2000 hours; temperature: 22°C±1°C; humidity: 55%±10%). Experimental groups were designed as follows: a combined control group and two exposed groups in two different series, series 1 and series 2, exposed at different aerosol concentrations, as described in the next section. Twenty-four animals were used for uranium concentration analysis by ICP-MS (n=8 per group: one control group and two exposed groups, series 1 and series 2). Eighteen animals were used for uranium in situ localization using high-resolution microscopy (n=6 per group: control group and 2 exposed groups, series 1 and 2). Animal experiments were performed in compliance with French and European regulations on protection of animals used for scientific purposes (EC Directive 2010/63/EU and French Decree 2013–118). They were approved by Ethics Committee #81 and authorized by the French Ministry of Research (reference 01017.01).Aerosol Generation and Inhalation ProcedureUO4 powder (Orano NC) is depleted in U235 as compared with natural uranium, and it contains the nonnatural U236 isotope. The isotopic composition by mass of the UO4 powder was isotope 238 of uranium U238=99.55%, U236=0.051%; U235=0.39%, and U234=0.0047%.The nose-only inhalation system and the procedure have been previously described (Tournier et al. 2009). Our inhalation glove box is made of three parts: the aerosol generator chamber containing a rotating brush generator (RBG 1000; Palas) used for aerosol generation from dry powder. The nose-only tubes are connected to the aerosol exposure chamber. The outlet of the RBG 1000 is directly connected to the top of the exposure chamber by antistatic tubing. The chamber is equipped with high-efficiency exhaust filters in order to prevent contamination of the glove box. The noses of the rats were in direct contact with aerosols in the exposure chamber connected with the nose-only tubes. The third part contains the devices used to perform aerosol metrology. An Aerodynamic Particle Sizer® (APS™ Spectrometer 3321; TSI) combined with a diluter was used to determine particle size distribution and for real-time monitoring of the aerosol concentration in the inhalation chamber. The reference aerosol concentration in the inhalation chamber was measured by sampling particles on cellulose acetate membrane filters (0.8μm pore size, 25mm diameter; Millipore) with a constant flow rate equal to 2L/min. The uranium mass concentration was determined by weight and ICP-MS analysis.Before exposure via inhalation, all animals were progressively acclimatized to the tubes over a period of 3 wk in order to avoid the stress induced by the inhalation procedure (three progressive sessions per week: the first session duration was 10 min, and length was incremented by 10 min at each session to reach 1 h, which included the total length of the procedure, inhalation exposure, and transfer inside the glove box). Rats were exposed to uranium aerosols for 30 min. Control rats were also maintained in tubes and exposed to ambient air for 30 min. All animals were euthanized 4 h after the end of inhalation, and selected tissues were collected. Two different aerosol concentrations were selected in order to increase the chance of being above the detection limits of the imaging techniques used in our study. Our previous studies provided us robust feedback on the minimal exposure concentrations that could be detected without affecting the ultrastructure of the olfactory epithelium (Tournier et al. 2009; Ibanez et al. 2014). The mean aerosol concentrations during exposure were 218 mg/m3 for series 1 and 545 mg/m3 for series 2. The series 2 exposure concentration is within the range found in our previous work (Monleau et al. 2005, Tournier et al. 2009). The aim was also to expose animals to a lower (half) concentration in series 1. The aerodynamic mass median diameter was 4.6μm for series 1 and 4.4μm for series 2.Aerosol size distribution was also characterized by TEM analysis and image processing. To perform image processing and particle size distribution analysis, we used the advanced software provided with the Morphologi G3 instrument (Malvern Panalytical) (Malvern, version 7). The aerosol sample analyzed was collected directly on the TEM grids and deposited at the surface of the filter used for mass concentration measurement. Results are described in Figure 1.Figure 1. Transmission electron microscopy (TEM) microphotograph and particle size distributions in uranium tetraoxide (UO4) aerosol. (A) Representative TEM microphotograph of UO4 particle (scale bar: 10μm). (B) Particle volume size distribution. (C) Particle count size distribution. The particle size distribution from the particle image processing is expressed according to the circumference-equivalent diameter (CE diameter) of particles. (B) Shows the CE diameter size distribution in terms of particle volume (calculated from CE diameter). Results show a median CE diameter equal to 1.4μm with a volume size distribution spread between 0.1μm and 4μm [red bars represent the volume fraction (%), green line graph represents the cumulative fraction (%)]. (C) Represents the distribution of CE diameter according to particle number. The count median diameter was equal to 0.4μm and the size distribution obtained revealed that, in terms of number, 90% of particles had a CE diameter below 1μm [red bars represent the number fraction (%); green line graph represents the cumulative fraction (%)].Sample Collection and Inductively Coupled Plasma Mass Spectrometry Analysis (ICP-MS)Rats were deeply anesthetized by inhalation of 5% isoflurane and 95% air and sacrificed by exsanguination 4 h after inhalation. This time point was based on the study performed with the intranasal instillation model (Ibanez et al. 2014), and it coincides with a peak of accumulation of uranium in the brain after nasal exposure in rodent models (Ibanez et al. 2014; Petitot et al. 2013). The OE was dissected out, weighed, and stored at −80°C. Selected brain structures were microdissected after the brain was removed and placed on ice: OB, FC, HIP, Cer, and BS. As for OE, samples were weighed and stored at −80°C. In order to measure uranium concentration, samples were first dissolved in 8mL of 69% nitric acid HNO3 (Aristar®; VWR) and 2mL of 30% hydrogen peroxide (NORMAPUR®; VWR) using a microwave oven (Ethos Start D Microwave Digestion System 1000W; Milestone). The nitric acid digestion mixture was warmed to 180°C over 15 min and then held for a further 10 min at the same temperature in the microwave oven at 1,000W using the digestion rotor system. Samples were then evaporated on heating plates under a fume hood and dissolved in 3mL of 20% HNO3. All samples from each different brain structure were diluted appropriately (1/10) and analyzed for elemental uranium concentration using an ICP-MS (X series II, Thermo Electron with S-Option; Thermo Fisher Scientific). Bismuth was used as the internal standard (Claritas PPT Grade, catalog number: SPEX CertiPrep™ CLBI2-1AY, purity: 97.99%, 10mg/L in 2% HNO3; Fisher Scientific). The quantification limit of uranium measured by ICP-MS was 1 ng/L for U238 and U235.Biological Sample Preparation for Secondary Ion Mass Spectrometry (SIMS) Microscopy and Transmission Electron Microscopy Coupled with Energy-Dispersive X-ray Spectroscopy (TEM-EDX) AnalysisOlfactory neuroepithelia were dissected out 4 h after inhalation as described previously, and the tissue was submitted for a standard chemical fixation procedure. Samples were fixed with a solution containing 2.5% glutaraldehyde for 1 h at room temperature, dehydrated in ethanol baths, and permeabilized with a propylene oxide/Epon mixture. No osmium or uranyl acetate was used to counterstain the tissue samples in order to avoid artefacts for both the SIMS and TEM-EDX observations and analyses. This procedure allowed the olfactory epithelium sections to be observed in their physiological state. Finally, samples were embedded in pure Epon-type resin (Electron Microscopy Sciences, ref 14900, Hatfield TA19440). Serial transverse thin sections (900 nm) embedded in resin were cut and laid on polished ultrapure silicon holders for SIMS analysis (to avoid relief effects and minimize charge effects), or on glass slides and stained with toluidine blue for histological controls with an optical microscope. Ultrathin transverse sections (70 nm) were cut and collected on copper grids for TEMS.Secondary Ion Mass Spectrometry (SIMS) MicroscopyThe aim of SIMS microscopy is the elemental and isotopic analysis of a solid surface by an ion beam coupled with a mass spectrometer. This technique is based upon the sputtering of a few atomic layers from the surface of a sample, induced by the bombardment of focused primary ions (O2+, O−, Cs+, or Ar+) with sufficiently high energy [several kiloelectron volts (KeV)]. These primary ions penetrate the solid surface and transfer some of their kinetic energy to the target particles, creating collision cascades that induce the emission of surface particles (atoms or molecules) in a charged or uncharged state. The secondary ions are representative of the elemental and isotopic composition of the bombarded analyzed area. They are accelerated and analyzed with a mass spectrometer (electrostatic sector and magnetic sector) on the basis of the mass-to-charge ratio. The sputtered ions stemming from each point of the bombarded surface are focused into an image by an immersion objective lens. The SIMS analysis was performed using a CAMECA IMS 4F E7 instrument. For this study, O2+ beam bombardment was used to enhance the ionization field of electropositive species such as uranium [Energy (E)=12 KeV; Intensity (I)=500 picoampere (pA)]. In this scanning microscope, the primary beam was focused into a small shaft (around 0.5μm), which scans the sample surface. The collected secondary ions were measured with an electron multiplier and also sequentially converted into an image. Mass resolution could reach 10,000 (M/ΔM), and the lateral resolution of the imaging was 0.5μm. For each area analyzed, mass spectra at around the mass of U238 and ion images were obtained. Na+23 images gave the histological structure of the sample, and U+238 images showed uranium fixation within the structures. Analyses were performed as follows: two controls, two animals of series 1, and five animals of series 2 were analyzed. For each animal, an average of 10 areas (200×200μm) were fully mapped for Na+23 and U+238.Transmission Electron Microscopy Coupled With Energy-Dispersive X-ray Spectroscopy (TEM-EDX) AnalysisCompared with light microscopy, TEM uses an electron beam instead of light, thus providing optimal resolution and revealing the finest details of an internal structure at high magnification, here within the olfactory mucosa. The condenser lens of the microscope allows restriction of the electron beam into a thin and coherent beam by modulating its aperture. The beam then strikes the ultrathin sections collected on a grid. The resulting image on the charge-coupled device (CCD) camera depends upon the thickness and electron transparency of the tissue section. The contrast can be modulated using high-angle diffracted electrons and projector lenses, which allow the image to be focused and enlarged. Dark areas in the image correspond to areas where few electrons are transmitted and lighter areas where more electrons can go through the specimen. The power of the electron beam is expressed in KeV. In our study, the ultrastructure observations of the olfactory mucosa ultrathin sections were performed using the Electron Microscopy Platform at the Muséum National d’Histoire Naturelle. The high-resolution transmission electron microscope used was the following: HT7700 model, 120 kV (Hitachi) with its associated STEM (scanning TEM) module and CCD camera. The aim of TEM microscopy is to provide precise ultrastructural cytoarchitecture of the olfactory epithelium. Because nanoscale particle detection has a restricted detection limit, analyses were then focused on animals exhibiting the relative higher concentration of uranium (as seen in SIMS analysis spectra). They were performed as follows: two controls and three animals of series 2 were analyzed. For each animal, an average of 4 TEM grids with 2 to 3 sections on each grid were observed under the microscope, resulting in an average of 10 sections analyzed per animal.The elemental composition of the particles detected in our ultrathin sections of the olfactory mucosa was then analyzed with an EDX module. The principle of the EDX analysis relies on an electron beam that strikes the specimen within a selected area. This action results in the production of X-rays having the specific energies of the chemical elements present on the analyzed surface. The electron microscope is combined with an EDX detector (Thermo Fisher Scientific). EDX analysis was performed at 80 kV, and specific uranium energies were revealed for M and Lα (M and L refers to the name of atomic layers) at 3.1 and 13.6 KeV.Statistical AnalysisResults from the ICP-MS measurements are expressed as mean±standard deviation (SD). Nonparametric statistics were chosen to analyze ICP-MS results as the normality test (Shapiro-Wilk test) failed (p<0.05). Uranium concentrations in the exposed groups were compared with the control for each brain structure using a Kruskal-Wallis one-way analysis of variance (ANOVA) on ranks, followed by a Mann-Whitney rank-sum test to compare each uranium condition with the control. The Kruskal-Wallis test was also performed to test if uranium concentration variations between the selected brain structures within the same group were different (Table 1; Figure 2). The level of significance was established for p≤0.05. In addition, statistical analysis using the Poisson distribution was performed in order to estimate the probability of detection of UO4 particles of 0.5μm and 1μm diameter in a given tissue volume of the neuroepithelium analyzed by use of SIMS microscopy.Table 1 Uranium concentrations in selected brain structures as measured by inductively coupled plasma mass spectrometry (ICP-MS).Table 1 has four columns, namely, structures, control, series 1 and series 2 for uranium concentrations (nanograms per gram tissue).Uranium concentrations (ng/g tissue)StructuresControlSeries 1Series 2OB1.51±0.1917.95±13.3415.31±4.60FC2.01±0.437.44±1.8912.33±2.17HIP1.21±0.084.70±1.009.31±3.15Cer0.47±0.052.45±0.475.25±1.09BS0.87±0.123.86±0.598.25±2.32Note: Data are expressed as mean±SD (Experimental groups: a combined control group and 2 exposed groups, series 1 and series 2, exposed at 218 mg/m3 and 545 mg/m3, respectively; n=8 per group). BS, brainstem; Cer, cerebellum; FC, frontal cortex; HIP, hippocampus; OB, olfactory bulbs.Figure 2. Statistical analysis comparing uranium concentrations in selected brain structures. Results are presented for adult male Sprague-Dawley rats exposed to a uranium tetraoxide (UO4) aerosol via inhalation, and samples were collected 4 h after the end of the exposure (n=8 per group: a control group and two exposed groups; series 1 and 2). Data are expressed as mean+standard deviation (SD). *, significant difference between a control brain structure and its anatomical counterpart in the control group from the series 1 or 2 exposed groups [nonparametric analysis of variance (ANOVA) ***p≤0.001 followed by Mann-Whitney ***p≤0.001 for each structure compared with controls). #, significant difference b" @default.
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- W2978403702 title "Evaluation of the Nose-to-Brain Transport of Different Physicochemical Forms of Uranium after Exposure <i>via</i> Inhalation of a UO4 Aerosol in the Rat" @default.
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