International Stroke Conference 2025  /  Translational Basic Science Moderated Digital Posters I  /  Reversibility of White Matter Damage, Neuroinflammation, and Oxidative Stress from Diesel Exhaust
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American Heart Association

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Final ID: DP27

Reversibility of White Matter Damage, Neuroinflammation, and Oxidative Stress from Diesel Exhaust

Abstract Body: Introduction
Air pollution derived from diesel exhaust has been linked with cognitive decline and cerebrovascular diseases. In previous studies, subacute diesel exhaust exposure has been shown to increase neurotoxicity and white matter damage; however, few studies have modeled the effects of air quality improvement. Our previous data from the same cohort showed persistent microglial activation (Iba-1) after an 8-week recovery period. The objective of this study was to further investigate the extent of recovery after neurotoxic diesel exhaust particulate (DEP) exposure.

Methods
Female and male 8-week-old C57BL/6 mice were exposed to inhaled Filtered Air (FA) and DEP (NIST SRM 2975) at concentration of 100μg/m3. There were three arms in this study: 1) 8 weeks of FA or DEP exposure (n=16/group); 2) 8 weeks of FA or DEP exposure followed by 8 weeks of recovery (n=16/group); and 3) 16 weeks of FA or DEP exposure (n=16/group). Mice were humanely euthanized and brain hemispheres sectioned at 5 µm. Corpus callosum levels of C5 complement protein, C5a anaphylatoxin, 4-hydroxynonenal (4-HNE), 8-Oxo-2'-deoxyguanosine (8-OHDG), and degraded myelin basic protein (dMBP) were assayed via immunofluorescence.

Results
The 8-week DEP group demonstrated increases in C5 (+39%), C5a (+45%), 4-HNE (+107%), 8-OHDG (+26%), and dMBP (+118%) in comparison to the 8-week FA group. The 8-week DEP recovery group demonstrated no significant elevation in C5, C5a, 4-HNE, and 8-OHDG in comparison to the 8-week FA recovery group. However, dMBP remained elevated (+87%) after in the 8-week DEP recovery group compared to the 8-week FA recovery group. The 16-week DEP group demonstrated increases in C5 (+44%), C5a (+58%), 4-HNE (+106%), 8-OHDG (+57%), and dMBP (+94%) in comparison to the 16-week FA group (p-values in Figure 1).

Conclusions
DEP exposure results in increased oxidative stress, neuroinflammation, and myelin breakdown at 8 weeks and 16 weeks. Unlike neuroinflammation and oxidative stress that recovered, white matter damage showed a persistent effect after an 8-week washout period. Combined with our previous data on persistent microglia activation, this suggests that prolonged neuroimmune response may contribute to the white matter injury that persists several months after DEP exposure termination.
  • Tang-tan, Angela  ( Keck School of Medicine of USC , Los Angeles , California , United States )
  • Shkirkova, Kristina  ( Keck School of Medicine of USC , Los Angeles , California , United States )
  • Demetriou, Alexandra  ( Keck School of Medicine of USC , Los Angeles , California , United States )
  • Chen, Selena  ( Keck School of Medicine of USC , Los Angeles , California , United States )
  • Daggupati, Sindhu  ( Keck School of Medicine of USC , Los Angeles , California , United States )
  • Bent, Christine  ( Keck School of Medicine of USC , Los Angeles , California , United States )
  • Zhao, Lifu  ( Keck School of Medicine of USC , Los Angeles , California , United States )
  • Thorwald, Max  ( Leonard Davis School of Gerontology of USC , Los Angeles , California , United States )
  • Godoy-lugo, Jose  ( Leonard Davis School of Gerontology of USC , Los Angeles , California , United States )
  • Sauri, Ariel  ( Leonard Davis School of Gerontology of USC , Los Angeles , California , United States )
  • Sioutas, Constantinos  ( Viterbi School of Engineering of USC , Los Angeles , California , United States )
  • Pike, Christian  ( Leonard Davis School of Gerontology of USC , Los Angeles , California , United States )
  • Finch, Caleb  ( Leonard Davis School of Gerontology of USC , Los Angeles , California , United States )
  • Mack, William  ( Keck School of Medicine of USC , Los Angeles , California , United States )
    • Author Disclosures:
    Angela Tang-Tan: DO NOT have relevant financial relationships | Ariel Sauri: No Answer | Constantinos Sioutas: DO NOT have relevant financial relationships | Christian Pike: DO have relevant financial relationships ; Research Funding (PI or named investigator):Estetra SRL:Active (exists now) | Caleb Finch: DO NOT have relevant financial relationships | William Mack: DO have relevant financial relationships ; Employee:UNIVERSITY OF SOUTHERN CALIFORNIA:Active (exists now) ; Individual Stocks/Stock Options:Vastrax:Active (exists now) ; Individual Stocks/Stock Options:Q'Apel:Active (exists now) ; Individual Stocks/Stock Options:Stream Biomedical:Active (exists now) ; Individual Stocks/Stock Options:Spartan Micro:Active (exists now) ; Individual Stocks/Stock Options:Egret:Active (exists now) ; Consultant:Stryker:Active (exists now) ; Consultant:Medtronic:Active (exists now) ; Consultant:Imperative Care:Active (exists now) ; Individual Stocks/Stock Options:Endostream:Active (exists now) ; Individual Stocks/Stock Options:Radical Catheters:Active (exists now) ; Individual Stocks/Stock Options:Borvo:Active (exists now) ; Individual Stocks/Stock Options:Viseon:Active (exists now) | Kristina Shkirkova: DO NOT have relevant financial relationships | Alexandra Demetriou: DO NOT have relevant financial relationships | Selena Chen: DO NOT have relevant financial relationships | Sindhu Daggupati: DO NOT have relevant financial relationships | Christine Bent: No Answer | Lifu Zhao: DO NOT have relevant financial relationships | Max Thorwald: DO NOT have relevant financial relationships | Jose Godoy-Lugo: DO NOT have relevant financial relationships
Meeting Info:

International Stroke Conference 2025

2025

Los Angeles, CA

Session Info:

Translational Basic Science Moderated Digital Posters I

Wednesday, 02/05/2025 , 03:00PM - 03:30PM

Moderated Digital Poster Abstract Session

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