4.8 Article

Passage of exogeneous fine particles from the lung into the brain in humans and animals

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2117083119

Keywords

air pollution; particulate matters; ambient exposure; brain health; particle retention

Funding

  1. National Natural Science Foundation of China [91943301, 21906175, 22150006, 21920102007, 22021003]
  2. Beijing Natural Science Foundation [8191002]
  3. Shandong Province Natural Science Foundation [ZR202010300086]
  4. European Commission [814572, 814425, 731032]

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The study revealed the potential pathway of exogenous particles entering the central nervous system, supporting the association between the inhalation of exogenous particles and their transport to brain tissues. Additionally, experimental results indicated that inhaled particles have a much slower retention rate in the brain compared to other major metabolic organs.
There are still significant knowledge gaps in understanding the intrusion and retention of exogeneous particles into the central nervous system (CNS). Here, we uncovered various exogeneous fine particles in human cerebrospinal fluids (CSFs) and identified the ambient environmental or occupational exposure sources of these particles, including commonly found particles (e.g., Fe- and Ca-containing ones) and other compositions that have not been reported previously (such as malayaite and anatase TiO2), by mapping their chemical and structural fingerprints. Furthermore, using mouse and in vitro models, we unveiled a possible translocation pathway of various inhaled fine particles from the lung to the brain through blood circulation (via dedicated biodistribution and mechanistic studies). Importantly, with the aid of isotope labeling, we obtained the retention kinetics of inhaled fine particles in mice, indicating a much slower clearance rate of localized exogenous particles from the brain than from other main metabolic organs. Collectively, our results provide a piece of evidence on the intrusion of exogeneous particles into the CNS and support the association between the inhalation of exogenous particles and their transport into the brain tissues. This work thus provides additional insights for the continued investigation of the adverse effects of air pollution on the brain.

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