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

• DOI: 10.1093/toxsci/kfab147
• Publication Date: 2021-11-30T12:08:41Z
• Authors: David Scieszka; Russell Hunter; Jessica Begay; Marsha Bitsui; Yan Lin; Joseph Galewsky; Masako Morishita; Zachary Klaver; James Wagner; Jack R Harkema; Guy Herbert; Selita Lucas; Charlotte McVeigh; Alicia Bolt; Barry Bleske; Christopher G Canal; Ekaterina Mostovenko; Andrew K Ottens; Haiwei Gu; Matthew J Campen; Shahani Noor
• Keywords: Proinflammatory cytokine; Inhalation exposure

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