Integrated network toxicology and In Vitro/In Vivo experiments reveal molecular mechanisms of perfluorooctanoic acid exposure affecting intracerebral hemorrhage prognosis

The incidence of intracerebral hemorrhage (ICH) is rising, and environmental chemical exposure is now recognized as a major factor contributing to poor cerebrovascular outcomes. Perfluorooctanoic acid (PFOA), a common perfluoroalkyl and polyfluoroalkyl substance (PFAS), has been extensively applied in industrial and consumer products. Despite its gradual phase-out since 2005, PFOA remains prevalent in water sources worldwide. Accumulating evidence links chronic PFOA exposure, particularly during early development, to a higher risk of neurological impairment. However, the neurotoxic mechanisms underlying its effects remain unclear. The present study evaluated the impact of prolonged exposure to environmentally relevant concentrations of PFOA on ICH prognosis. In vivo experiments showed that PFOA exposure enlarged hematomas, increased neuronal death, and promoted microglial aggregation, thereby accelerating disruption of the blood-brain barrier. In vitro findings indicated that PFOA pretreatment suppressed neurofilament and axonal protein expression in HT22 cells and directly bound to AKT1 in microglia, activating the AKT/STAT/MMP pathway and amplifying proinflammatory responses. These findings indicate that long-term PFOA exposure may be associated with worsened prognosis of ICH as a potential environmental risk factor. The extensive use of PFOA in consumer products warrants careful reassessment of its safety and regulatory standards.