Combined Exposure to High-Cholesterol Diet and PM2.5: Brain Injury and Regulatory Mechanism of HIF-1α in ApoE−/− Female Mice

High-cholesterol diet (HCD) and fine particulate matter (PM2.5) are related to stroke. However, little is known about the combined effects of stroke, especially for females. This study investigated the brain injuries in Apolipoprotein E−/− (ApoE−/−) female mice exposed to HCD plus PM2.5 for 6 months. The protein levels of the genes related to stroke and the blood–brain barrier (BBB) in different groups of mice were measured. The molecular regulation mechanisms were explored. The results showed that HCD and PM2.5 co-exposure altered brain–body weight ratio, behavior, brain pathology, and inflammatory markers in mice relative to exposure to HCD or PM2.5 alone. Co-exposure significantly changed the expressions of HIF-1α and the key genes in its signaling pathway in the brains of mice compared to the single exposure. It suggests that the HIF-1α pathway exerts an important regulatory role in brain injury and behavioral abnormality in female mice after 6-month exposure to HCD plus PM2.5, which are potential mechanisms for HCD and PM2.5-triggering stroke in female individuals.