Neuroinflammatory and Metabolomic Temporal Dynamics Following Wood Smoke Inhalation

Author:

Scieszka David1,Jin Yan2,Noor Shahani3,Barr Ed1,Garcia Marcus1,Begay Jessica1,Herbert Guy1,Hunter Russell P1,Bhaskar Kiran3,Kumar Rahul4,Gullapalli Rama4,Bolt Alicia1,McCormick Mark A.5,Bleske Barry6,Gu Haiwei2,Campen Matthew1

Affiliation:

1. University of New Mexico, College of Pharmacy

2. Florida International University, Center for Translational Sciences

3. University of New Mexico, Department of Molecular Genetics and Microbiology

4. University of New Mexico, Department of Pathology

5. University of New Mexico, Department of Biochemistry and Molecular Biology

6. University of New Mexico, Department of Pharmacy Practice and Administrative Science

Abstract

Abstract Smoke from wildland fires has been shown to produce neuroinflammation in preclinical models, characterized by neural infiltrations of neutrophils and monocytes, as well as altered neurovascular endothelial phenotypes. To address the longevity of such outcomes, the present study examined the neuroinflammatory and metabolomic temporal dynamics after inhalation exposures from biomass-derived smoke. 2-month-old female C57BL/6J mice were exposed to wood smoke every other day for two weeks at an average exposure concentration of 0.5mg/m3. Subsequent serial euthanasia occurred at 1-, 3-, 7-, 14-, and 28-days post-exposure. Flow cytometry of right hemispheres revealed two endothelial populations of PECAM (CD31), high and medium expressors, with wood smoke inhalation causing an increased proportion of PECAMHi. These populations of PECAMHi and PECAMMed were associated with an anti-inflammatory and pro-inflammatory response, respectively, and their inflammatory profiles were largely resolved by the 28-day mark. However, activated microglial populations (CD11b+/CD45low) remained higher in wood smoke-exposed mice than controls at day 28. Infiltrating neutrophil populations decreased to levels below controls by day 28. However, the MHC-II expression of the peripheral immune infiltrate remained high, and the population of neutrophils retained an increased expression of CD45, Ly6C, and MHC-II. Utilizing an unbiased approach examining the metabolomic alterations, we observed notable hippocampal perturbations in neurotransmitter and signaling molecules like glutamate, quinolinic acid, and 5-α-dihydroprogesterone. Utilizing a targeted panel designed to explore the aging-associated NAD+ metabolic pathway, wood smoke exposure drove fluctuations and compensations across the 28-day time course, ending with decreased hippocampal NAD+ abundance at day 28. Summarily, these results indicate a highly dynamic neuroinflammatory environment, with potential resolution extending past 28 days, the implications of which may include long-term behavioral changes, systemic and neurological sequalae directly associated wtith wildfire smoke exposure.

Publisher

Research Square Platform LLC

Reference56 articles.

1. Wildfires and Acres | National Interagency Fire Center [Internet]. [cited 2023 Jan 13]. Available from: https://www.nifc.gov/fire-information/statistics/wildfires

2. Review of the health effects of wildland fire smoke on wildland firefighters and the public;Adetona O;Inhal Toxicol,2016

3. Critical Review of Health Impacts of Wildfire Smoke Exposure;Reid CE;Environ Health Perspect,2016

4. Smoke and the eyes: A review of the harmful effects of wildfire smoke and air pollution on the ocular surface;Jaiswal S;Environ Pollut Barking Essex 1987,2022

5. Respiratory symptoms following wildfire smoke exposure: airway size as a susceptibility factor;Mirabelli MC;Epidemiol Camb Mass,2009

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