Kristina Shkirkova, Alexandra N Demetriou, Saman Sizdahkhani, Krista Lamorie-Foote, Hongqiao Zhang, Manuel Morales, Selena Chen, Lifu Zhao, Arnold Diaz, Jose A Godoy-Lugo, Beryl Zhou, Nathan Zhang, Andrew Li, Wendy Mack, Constantinos Sioutas, Max A Thorwald, Caleb Finch, Christian J Pike, William Mack
Background: Air pollution particulate matter (PM) exposure and chronic cerebral hypoperfusion (CCH) contribute to white matter toxicity through shared mechanisms of neuroinflammation, oxidative stress, and myelin breakdown. Prior studies showed that exposure of mice to joint PM and CCH caused supra-additive injury to corpus callosum white matter. This study examines the role of toll-like receptor 4 (TLR4) signaling in mediating neurotoxicity and myelin damage observed in joint PM and CCH exposures. Methods: Experiments utilized a novel murine model of inducible monocyte/microglia-specific TLR4 knockout (i-mTLR4-ko)...
February 1, 2024: Stroke; a Journal of Cerebral Circulation