31 The neurotoxic threat of air pollution: a critical synthesis of behavioural and mechanistic evidence from rodent models

Abstract Air pollution is increasingly recognized as a potential driver of neurological dysfunction, yet animal experimental data remain methodologically fragmented. This review synthesizes evidence from 38 rodent studies investigating behavioural and mechanistic effects of inhaled pollutants, including fine particulate matter (PM₂.₅), ultrafine particles, diesel exhaust, gases, and engineered nanomaterials. Studies were identified through systematic searches of PubMed, Web of Science, and Scopus following PRISMA guidelines, and inclusion required behavioural assessment following inhalation or intranasal exposure. Data were extracted and categorized by pollutant class, exposure conditions, behavioural domain, and mechanistic endpoint. Across models, consistent impairments were found in learning, memory, mood, and social interaction, with variable susceptibility across sex, strain, and developmental stage. Mechanistic findings converge on neuroinflammation, oxidative stress, synaptic dysfunction, altered neurotransmission, and mitochondrial impairment, frequently accompanied by glial activation and blood–brain barrier disruption. These pathologies are concentrated in the hippocampus, prefrontal cortex, amygdala, and olfactory bulb, regions critical for cognition and emotion. Despite substantial heterogeneity in exposure paradigms and reporting standards, convergent behavioural and biological outcomes indicate a reproducible neurotoxic signal across pollutant types. Methodological assessment revealed limited chronic exposure models, inconsistent bias control, and historical exclusion of females. Future studies should address these constraints through environmentally realistic exposures, component-specific mechanistic designs, and harmonized behavioural endpoints. Overall, this synthesis integrates behavioural and mechanistic evidence demonstrating that inhaled particles can impair brain function through overlapping inflammatory and oxidative pathways, providing an integrated understanding for advancing particle neurotoxicity research.