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.