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Transport of Intranasally Instilled Fine Fe2O3 Particles into the Brain: Micro-distribution, Chemical States, and Histopathological Observation

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Abstract

It has been demonstrated that inhaled fine (d < 2.5 μm) and ultrafine (d < 100 nm) particles produce more severe toxicity than coarse particles. Some recent data support the concept that the central nervous system (CNS) may be a target for the inhaled fine particulates. This work describes initial observation of the transport of intranasally instilled fine ferric oxide (Fe2O3) particles in animal brain. The iron micro-distribution and chemical state in the mice olfactory bulb and brain stem on day 14 after intranasal instillation of fine Fe2O3 particle (280 ± 80 nm) suspension at a single dose of 40 mg/kg body weight were analyzed by synchrotron radiation x-ray fluorescence and x-ray absorption near-edge structure (XANES). The micro-distribution map of iron in the olfactory bulb and brain stem shows an obvious increase of Fe contents in the olfactory nerve and the trigeminus of brain stem, suggesting that Fe2O3 particles were possibly transported via uptake by sensory nerve endings of the olfactory nerve and trigeminus. The XANES results indicate that the ratios of Fe (III)/Fe (II) were increased in the olfactory bulb and brain stem. The further histopathological observation showed that the neuron fatty degeneration occurred in the CA3 area of hippocampus. Such results imply an adverse impact of inhalation of fine Fe2O3 particles on CNS.

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References

  1. Samet JM, Dominici FR, Curriero FCD, Coursac I, Zeger SL (2000) Fine particulate air pollution and mortality in 20 U.S. cities, 1987–1994. New Engl J Med 343:1742–1749

    Article  PubMed  CAS  Google Scholar 

  2. Katsouyanni K, Touloumi G, Spix C, Schwartz J, Balducci F, Medina S, Rossi G, Wojtyniak B, Sunyer J, Bacharova L, Schouten JP, Ponka A, Anderson HR (1997) Short-term effects of ambient sulphur dioxide and particulate matter on mortality in 12 European cities: results from the APHEA Project. Br Med J 314:1658–1663

    CAS  Google Scholar 

  3. Pope CA, Schwartz J, Ransom MR (1992) Daily mortality and PM10 pollution in Utah Valley. Arch Environ Health 47:211–217

    Article  PubMed  Google Scholar 

  4. Utell MJ, Frampton MW (2000) Acute health effects of ambient air pollution: the ultrafine particle hypothesis. J Aerosol Med 13:355–359

    PubMed  CAS  Google Scholar 

  5. Peters A, Wichmann HE, Tuch T, Heinrich J, Heyder J (1997) Respiratory effects are associated with the number of ultrafine particles. Am J Respir Crit Care Med 155:1376–1383

    PubMed  CAS  Google Scholar 

  6. Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Schulz H, Oberdörster G, Ziesenis A (2002) Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J Toxicol Environ Health 65(20):1513–1530

    Article  CAS  Google Scholar 

  7. Kreyling WG, Semmler-Behnke M, Moller W (2006) Ultrafine particle lung interactions: does size matter? J Aerosol Med 19:74–83

    Article  PubMed  CAS  Google Scholar 

  8. Sunderman EW Jr (2001) Nasal toxicity, carcinogenicity, and olfactory uptake of metals. Ann Clin Lab Sci 31:3–22

    PubMed  CAS  Google Scholar 

  9. Henriksson J, Tallkvist J, Tjälve H (1997) Uptake of nickel into the brain via olfactory neurons in rats. Toxicol Lett 91:153–162

    Article  PubMed  CAS  Google Scholar 

  10. Burd GD (1993) Morphologic study of the effects of intranasal zinc sulfate irrigation on the mouse olfactory epithelium and olfactory bulb. Microsc Res Tech 24:195–213

    Article  PubMed  CAS  Google Scholar 

  11. Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C (2004) Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16:437–445

    Article  PubMed  CAS  Google Scholar 

  12. DeLorenzo A (1970) The olfactory neuron and the blood–brain barrier. In: DeLorenzo A, Wolstenholme G, Knight J (eds) Taste and smell in vertebrates. CIBA Foundation Symposium Series. Churchill, London, pp 151–176

    Google Scholar 

  13. Korczynski RE (2000) Occupational health concerns in the welding industry. Appl Occup Environ Hyg 15:936–945

    Article  PubMed  CAS  Google Scholar 

  14. Thompson KJ, Shoham S, Connor JR (2001) Iron and neurodegenerative disorders. Brain Res Bull 55:155–164

    Article  PubMed  CAS  Google Scholar 

  15. Götz ME, Double K, Gerlach M, Youdim MBH, Riederer P (2004) The relevance of iron in the pathogenesis of Parkinson’s disease. Ann N Y Acad Sci 1012:193–208

    Article  PubMed  CAS  Google Scholar 

  16. Elder A, Gelein R, Silva V, Feikert T, Opanashuk L, Carter J, Potter R, Maynard A, Ito Y, Finkelstein J, Oberdörster G (2006) Translocation of inhaled ultrafine manganese oxide particles to the central nervous system. Environ Health Perspect 114:1172–1178

    Article  PubMed  CAS  Google Scholar 

  17. Rao DB, Wong BA, McManus BE, McElveen AM, James AR, Dorman DC (2003) Inhaled iron, unlike manganese, is not transported to the rat brain via the olfactory pathway. Toxicol Appl Pharmacol 193:116–126

    Article  PubMed  CAS  Google Scholar 

  18. Garcia-Verdugo JM, Llahi S, Farinas I, Martin V (1986) Laminar organization of the main olfactory bulb of Podarcis hispanica: an electron microscopic and Golgi study. J Hirnforsch 27:87–100

    PubMed  CAS  Google Scholar 

  19. Holstege G, Kuypers HGJM, Dekker JJ (1977) The organization of the bulbar fiber connections to the trigeminal, facial and hypoglossal motor nuclei. II. An autoradiographic tracing study in the cat. Brain 100:265–286

    Article  Google Scholar 

  20. Molavi DW (1997) Neuroscience tutorial, The Washington University School of Medicine Neuroscience Tutorial. Available from: http://thalamus.wustl.edu/course/

  21. Huang YY, Li GC, He W, Wu YR (1997) The progress of Beijing Synchrotron Radiation X-ray fluorescence microprobe analysis. Final Report of Institute of High Energy Physics, pp 317–319

  22. Bodian D, Howe HA (1941) The rate of progression of poliomyelitis virus in nerves. Bull Johns Hopkins Hosp 69:79–85

    Google Scholar 

  23. Hunter DD, Dey RD (1998) Identification and neuropeptide content of trigeminal neurons innervating the rat nasal epithelium. Neuroscience 83:591–599

    Article  PubMed  CAS  Google Scholar 

  24. Hunter DD, Undem BJ (1999) Identification of substance P content of vagal afferent neurons innervating the epithelium of the guinea pig trachea. Am J Respir Crit Care Med 159:1943–1948

    PubMed  CAS  Google Scholar 

  25. Fechter LD, Johnson DL, Lynch RA (2002) The relationship of particle size to olfactory nerve uptake of non-soluble form of manganese into brain. Neurotoxicology 23:177–183

    Article  PubMed  CAS  Google Scholar 

  26. Lee BJ, Weiss ML, Mosier D, Chowdhury SI (1999) Spread of bovine herpesvirus type 5 (BHV-5) in the rabbit brain after intranasal inoculation. J Neurovirology 5:474–484

    CAS  Google Scholar 

  27. Gianutsos G, Morrow GR, Morris JB (1997) Accumulation of manganese in rat brain following intranasal administration. Fundam Appl Toxicol 37:102–105

    Article  PubMed  CAS  Google Scholar 

  28. Parvizi J, Damasio A (2001) Consciousness and the brainstem. Cognition 79:135–160

    Article  PubMed  CAS  Google Scholar 

  29. Schaefer ML, Bottger B, Silver WL, Finger TE (2002) Trigeminal collaterals in the nasal epithelium and olfactory bulb: a potential route for direct modulation of olfactory information by trigeminal stimuli. J Comp Neurol 444:221–226

    Article  PubMed  Google Scholar 

  30. Lewis J, Bench G, Myers O, Tinner B, Staines W, Barr E, Divine KK, Barrington W, Karlsson J (2005) Trigeminal uptake and clearance of inhaled manganese chloride in rats and mice. Neurotoxicology 26:113–123

    Article  PubMed  CAS  Google Scholar 

  31. Malecki EA, Devenyi AG, Beard JL, Cornor JR (1999) Existing and emerging mechanisms for transport of iron and manganese to the brain. J Neurosci Res 56:113–122

    PubMed  CAS  Google Scholar 

  32. Moos T, Morgan EH (1998) Kinetics and distribution of [59Fe-125I]transferrin injected into the ventricular system of the rat. Brain Res 790:115–128

    Article  PubMed  CAS  Google Scholar 

  33. Longa SD, Pin S, Cortès R, Soldatov AV, Alpert B (1998) Fe-heme conformations in ferric myoglobin. Biophys J 75:3154–3162

    Article  PubMed  CAS  Google Scholar 

  34. Yoshida S, Ektessabi A, Fujisawa S (2001) XANES spectroscopy of a single neuron from a patient with Parkinson’s disease. J Synchrotron Radiat 8:998–1000

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the foundation of National Basic Research Program of China (2006CB705605), the Chinese Academy of Sciences, and the National Natural Science Foundation of China (10490180, 20475055, 10675139).

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Authors and Affiliations

  1. Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China

    Bing Wang, Wei Y. Feng, Meng Wang, Jun W. Shi, Hong Ouyang, Yu L. Zhao & Zhi F. Chai

  2. Graduate School of Chinese Academy of Sciences, Beijing, China

    Bing Wang, Meng Wang, Jun W. Shi & Fang Zhang

  3. Institute of Nuclear Technology, Shenzhen University, Shenzhen, China

    Zhi F. Chai

  4. Beijing Synchrotron Radiation Laboratory, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China

    Yu Y. Huang & Ya N. Xie

  5. College of Chemistry and Molecular Engineering, Peking University, Beijing, China

    Hai F. Wang & Jing Wang

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  1. Bing Wang
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Correspondence to Wei Y. Feng.

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Wang, B., Feng, W.Y., Wang, M. et al. Transport of Intranasally Instilled Fine Fe2O3 Particles into the Brain: Micro-distribution, Chemical States, and Histopathological Observation. Biol Trace Elem Res 118, 233–243 (2007). https://doi.org/10.1007/s12011-007-0028-6

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  • DOI: https://doi.org/10.1007/s12011-007-0028-6

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