Modeling the effects of air pollution on the brain: A review of in vitro PM2.5 exposure studies

Air pollution is recognized as a major environmental risk factor, with growing evidence that it affects the central nervous system in addition to the respiratory and cardiovascular systems. Epidemiological studies link chronic fine particulate matter (PM_2.5) exposure with cognitive decline, altered neurodevelopment, increased risk of neurodegenerative disease, and a range of psychiatric conditions, underscoring the need for mechanistic studies clarifying how PM_2.5 influences cells at the molecular level. In vitro models provide a controlled setting to investigate these interactions and have identified several key pathways involved in PM_2.5 neurotoxicity, including oxidative stress, neuroinflammation, and regulated cell death pathways. This review synthesizes the current body of in vitro research, evaluates commonly used model systems, and outlines how particle composition, culture conditions, and exposure parameters shape experimental outcomes. We outline major limitations in existing studies and highlight priorities for future research aimed at improving understanding of the neurological effects of PM_2.5 exposure.