PM2.5 exposure exacerbates seizure symptoms and cognitive dysfunction by disrupting iron metabolism and the Nrf2-mediated ferroptosis pathway

In recent years, air pollution has garnered global attention due to its ability to traverse borders and regions, thereby impacting areas far removed from the emission sources. While prior studies predominantly focused on the deleterious effects of PM2.5 on the respiratory and cardiovascular systems, emerging evidence has highlighted the potential risks of PM2.5 exposure to the central nervous system. Nonetheless, research elucidating the potential influences of PM2.5 exposure on seizures, specifically in relation to neuronal ferroptosis, remains limited. In this study, we investigated the potential effects of PM2.5 exposure on seizure symptoms and seizures-induced hippocampal neuronal ferroptosis. Our findings suggest that seizure patients residing in regions with high PM2.5 levels are more likely to disturb iron homeostasis and the Nrf2 dependent ferroptosis pathway compared to those living in areas with lower PM2.5 levels. The Morris Water Maze test, Racine scores, and EEG recordings in epileptic mice suggest that PM2.5 exposure can exacerbate seizure symptoms and cognitive dysfunction. Neurotoxic effects of PM2.5 exposure were demonstrated via Nissl staining and CCK-8 assays. Direct evidence of PM2.5-induced hippocampal neuronal ferroptosis was provided through TEM images. Additionally, increased Fe2+ and lipid ROS levels indirectly supported the notion of PM2.5-induced hippocampal ferroptosis. Therefore, our study underscores the necessity of preventing and controlling PM2.5 levels, particularly for patients with seizures.