Neuroinflammatory and Neurometabolomic Consequences From Inhaled Wildfire Smoke-Derived Particulate Matter in the Western United States

Toxicol Sci. 2022 Feb 28;186(1):149-162. doi: 10.1093/toxsci/kfab147.

Abstract

Utilizing a mobile laboratory located >300 km away from wildfire smoke (WFS) sources, this study examined the systemic immune response profile, with a focus on neuroinflammatory and neurometabolomic consequences, resulting from inhalation exposure to naturally occurring wildfires in California, Arizona, and Washington in 2020. After a 20-day (4 h/day) exposure period in a mobile laboratory stationed in New Mexico, WFS-derived particulate matter (WFPM) inhalation resulted in significant neuroinflammation while immune activity in the peripheral (lung, bone marrow) appeared to be resolved in C57BL/6 mice. Importantly, WFPM exposure increased cerebrovascular endothelial cell activation and expression of adhesion molecules (VCAM-1 and ICAM-1) in addition to increased glial activation and peripheral immune cell infiltration into the brain. Flow cytometry analysis revealed proinflammatory phenotypes of microglia and peripheral immune subsets in the brain of WFPM-exposed mice. Interestingly, endothelial cell neuroimmune activity was differentially associated with levels of PECAM-1 expression, suggesting that subsets of cerebrovascular endothelial cells were transitioning to resolution of inflammation following the 20-day exposure. Neurometabolites related to protection against aging, such as NAD+ and taurine, were decreased by WFPM exposure. Additionally, increased pathological amyloid-beta protein accumulation, a hallmark of neurodegeneration, was observed. Neuroinflammation, together with decreased levels of key neurometabolites, reflect a cluster of outcomes with important implications in priming inflammaging and aging-related neurodegenerative phenotypes.

Keywords: VCAM-1; microglia; neuroinflammation; neurovascular unit; particulate matter; smoke.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Air Pollutants* / analysis
  • Air Pollutants* / toxicity
  • Animals
  • Endothelial Cells
  • Mice
  • Mice, Inbred C57BL
  • Particulate Matter / analysis
  • Particulate Matter / toxicity
  • Smoke / adverse effects
  • United States
  • Wildfires*

Substances

  • Air Pollutants
  • Particulate Matter
  • Smoke