Cerebrovascular disease, as represented by stroke, was identified as one of the leading causes of death worldwide. Although air pollution was widely documented to be associated with stroke, the underlying mechanism of such adverse effects remained largely unknown. Cardiovascular effects triggered by air pollution were regarded as the dominant contributor to stroke pathogenesis, indicating the interconnected pathological basis of cardio-cerebrovascular multimorbidity in driving acute cerebrovascular events. By adopting the adverse outcome pathway as a pivotal tool, this review summarized air pollution-related effects on the cerebral blood flow into 3 aspects, namely, direct damage to the cerebrovascular system, systemic inflammation from the pulmonary to the cardiovascular system, and blood pressure changes mediated by the autonomic nervous system. After triggering molecular initiating events such as reactive oxygen species generation and sensory receptor activation, air pollutants may cause key events affecting the blood-brain barrier integrity, thrombosis, atherosclerosis, and hypertension, eventually leading to acute cerebrovascular events. This review underscored the critical role of cardio-cerebrovascular multimorbidity in air pollution-related cerebrovascular disease, suggesting a complex interplay of mechanisms affecting brain health. Even at a relatively low exposure level, air pollution remained a latent but modifiable risk factor for stroke, emphasizing the urgent need for interventions to mitigate this public health threat and timely risk factor management for high-risk individuals.
Keywords: PM2.5; adverse outcome pathway; air pollution; cerebrovascular disease; stroke.