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Abstract Details

Recovery After Acute Diesel Exhaust Inhalation Demonstrates Persistent Neuroinflammation and Sex-based Differences in Resolution of Neurotoxicity
Aging, Dementia, Cognitive, and Behavioral Neurology
P9 - Poster Session 9 (8:00 AM-9:00 AM)
9-014
Traffic-associated air pollution harms neurologic health and may exacerbate pathologies such as stroke and dementia. Epidemiologic studies demonstrate that reductions in pollution exposure may slow cognitive decline and decrease dementia risk. The underlying mechanisms of neurologic recovery after pollution exposure are not defined.
To characterize the molecular underpinnings of recovery following acute diesel exhaust particle (DEP) exposure.
Eight-week male and female C57BL/6 mice were exposed to five hours of filtered air (FA) or aerosolized DEP. One cohort (n = 32) of FA and DEP mice ­were promptly sacrificed while the other cohort (n =32) recovered in home cages for two weeks prior to euthanasia. Immunofluorescence was performed on corpus callosum samples to evaluate the presence of markers of oxidative stress (4-HNE and 8-OHdG), complement activity (C5 and C5a), white matter damage (dMBP), and microglial activation (Iba-1).
Acute DEP exposure caused elevations in 4-HNE, 8-OHdG, C5a, and Iba-1 (p < 0.05), but not in dMBP or C5. Two-week recovery allowed 4-HNE and 8-OHdG elevations to decline to near-control levels, whereas elevations in C5a and Iba-1 persisted. When analyzed by sex, female mice, but not males, exhibited persistent (yet down-trending) elevations in 4-HNE after recovery (p < 0.001). Females also demonstrated persistent Iba-1 elevations post-DEP recovery (p < 0.05), whereas males exhibited nonsignificant elevations.

Five-hour DEP exposure causes persistent neuroinflammation after two-week recovery, though acute rises in oxidative stress markers generally resolve within this timeframe. Females exhibit more persistent oxidative stress and microglial activation than males, suggesting that the rate of recovery following pollution reduction may differ by sex in humans. These findings present, to our knowledge, the first molecular characterization of neurologic recovery following short-term pollution inhalation. The persistence of neuroinflammation observed after a single DEP exposure raises important clinical considerations regarding patient exposures to pollutants during recovery from neurologic insults.

Authors/Disclosures
Alexandra N. Demetriou
PRESENTER
Miss Demetriou has nothing to disclose.
Selena Chen No disclosure on file
Kristina Shkirkova (USC) No disclosure on file
Hongqiao Zhang No disclosure on file
Krista Lamorie-Foote No disclosure on file
Isaiah Becerra No disclosure on file
Lifu Zhao No disclosure on file
Max Thorwald (University of Southern California) No disclosure on file
Jose Godoy No disclosure on file
Wendy Mack No disclosure on file
Constantinos Sioutas (University of Southern California) No disclosure on file
Caleb E Finch (University of Southern California) No disclosure on file
Christian Pike (Univ Southern Califronia) No disclosure on file
William Mack No disclosure on file