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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, and Behavioral Neurology
P9 - Poster Session 9 (8:00 AM-9:00 AM)
9-014
To characterize the molecular underpinnings of recovery following acute diesel exhaust particle (DEP) exposure.
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.
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 颅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 Selena Chen has nothing to disclose.
Kristina Shkirkova (USC) Kristina Shkirkova has nothing to disclose.
Hongqiao Zhang No disclosure on file
Krista Lamorie-Foote No disclosure on file
Isaiah Becerra No disclosure on file
Lifu Zhao Lifu Zhao has nothing to disclose.
Max Thorwald (University of Southern California) Max Thorwald has nothing to disclose.
Jose Godoy Jose Godoy has nothing to disclose.
Wendy Mack No disclosure on file
Constantinos Sioutas (University of Southern California) Constantinos Sioutas has nothing to disclose.
Caleb E Finch (University of Southern California) No disclosure on file
Christian Pike (Univ Southern Califronia) The institution of Christian Pike has received research support from Estetra SRL. Christian Pike has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with NIH CSR.
William Mack William Mack has received personal compensation for serving as an employee of NFL. William Mack has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Imperative Care. The institution of William Mack has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vanderbilt University (Stryker study) . William Mack has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for BMJ. William Mack has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Goza and Honnald LLC. William Mack has stock in egret therapeutics. William Mack has stock in Borvo. William Mack has stock in Radical Catheters. William Mack has stock in Vastrax. William Mack has stock in Q'Apel. William Mack has stock in Viseon. William Mack has stock in Stream Biomedical. William Mack has stock in Spartan Micro. William Mack has stock in Endostream. The institution of William Mack has received research support from National Institutes of Health.