Translocation of inhaled ultrafine particles to the brain

Günter Oberdörster, Z. Sharp, V. Atudorei, A. Elder, R. Gelein, W. Kreyling, Christopher Cox

Research output: Contribution to journalArticle

Abstract

Ultrafine particles (UFP, particles 13C particles (CMD = 36 nm; GSD = 1.66) from [13C] graphite rods by electric spark discharge in an argon atmosphere at a concentration of 160 μg/m3. Rats were exposed for 6 h, and lungs, cerebrum, cerebellum and olfactory bulbs were removed 1, 3, 5, and 7 days after exposure. 13C concentrations were determined by isotope ratio mass spectroscopy and compared to background 13C levels of sham-exposed controls (day 0). The background corrected pulmonary 13C added as ultrafine 13C particles on day 1 postexposure was 1.34 μg/lung. Lung 13C concentration decreased from 1.39 μg/g (day 1) to 0.59 μg/g by 7 days postexposure. There was a significant and persistent increase in added 13C in the olfactory bulb of 0.35 μg/g on day 1, which increased to 0.43 μg/g by day 7. Day 1 13C concentrations of cerebrum and cerebellum were also significantly increased but the increase was inconsistent, significant only on one additional day of the postexposure period, possibly reflecting translocation across the blood-brain barrier in certain brain regions. The increases in olfactory bulbs are consistent with earlier studies in nonhuman primates and rodents that demonstrated that intranasally instilled solid UFP translocate along axons of the olfactory nerve into the CNS. We conclude from our study that the CNS can be targeted by airborne solid ultrafine particles and that the most likely mechanism is from deposits on the olfactory mucosa of the nasopharyngeal region of the respiratory tract and subsequent translocation via the olfactory nerve. Depending on particle size, >50% of inhaled UFP can be depositing in the nasopharyngeal region during nasal breathing. Preliminary estimates from the present results show that ∼20% of the UFP deposited on the olfactory mucosa of the rat can be translocated to the olfactory bulb. Such neuronal translocation constitutes an additional not generally recognized clearance pathway for inhaled solid UFP, whose significance for humans, however, still needs to be established. It could provide a portal of entry into the CNS for solid UFP, circumventing the tight blood-brain barrier. Whether this translocation of inhaled UFP can cause CNS effects needs to be determined in future studies.

Original languageEnglish (US)
Pages (from-to)437-445
Number of pages9
JournalInhalation Toxicology
Volume16
Issue number6-7
DOIs
StatePublished - Jun 2004
Externally publishedYes

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Olfactory Bulb
Brain
Olfactory Nerve
Olfactory Mucosa
Lung
Cerebrum
Blood-Brain Barrier
Cerebellum
Rats
Graphite
Argon
Electric sparks
Atmosphere
Nose
Particle Size
Isotopes
Respiratory System
Primates
Axons
Rodentia

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Oberdörster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Kreyling, W., & Cox, C. (2004). Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicology, 16(6-7), 437-445. https://doi.org/10.1080/08958370490439597

Translocation of inhaled ultrafine particles to the brain. / Oberdörster, Günter; Sharp, Z.; Atudorei, V.; Elder, A.; Gelein, R.; Kreyling, W.; Cox, Christopher.

In: Inhalation Toxicology, Vol. 16, No. 6-7, 06.2004, p. 437-445.

Research output: Contribution to journalArticle

Oberdörster, G, Sharp, Z, Atudorei, V, Elder, A, Gelein, R, Kreyling, W & Cox, C 2004, 'Translocation of inhaled ultrafine particles to the brain', Inhalation Toxicology, vol. 16, no. 6-7, pp. 437-445. https://doi.org/10.1080/08958370490439597
Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W et al. Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicology. 2004 Jun;16(6-7):437-445. https://doi.org/10.1080/08958370490439597
Oberdörster, Günter ; Sharp, Z. ; Atudorei, V. ; Elder, A. ; Gelein, R. ; Kreyling, W. ; Cox, Christopher. / Translocation of inhaled ultrafine particles to the brain. In: Inhalation Toxicology. 2004 ; Vol. 16, No. 6-7. pp. 437-445.
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