Mercuric Chloride‐Mediated Neurotoxicity in Chicken Embryos: Disruption of the Blood–Brain Barrier Integrity and Iron Overload‐Induced Ferroptosis

ABSTRACT Mercuric chloride (HgCl 2 ) is an environmental pollutant with neurotoxicity. The blood–brain barrier (BBB) serves as a critical protective interface, shielding the brain from exposure to heavy metals and maintaining neurological homeostasis. Ferroptosis, a programmed cell death initiated by iron‐dependent lipid peroxidation, was recently reported to be associated with various neurological disorders. Nevertheless, the relationship between HgCl 2 ‐induced neurotoxicity, BBB dysfunction, and ferroptosis remains unclear. This study investigated the effects of embryonic exposure to HgCl 2 (35, 50, and 65 μg/kg) on brain tissue and the underlying mechanisms. These results demonstrated that HgCl 2 exposure induced brain injury by compromising BBB integrity. Intriguingly, we identified ferroptosis as a central mechanism contributing to this damage, supported by the observation of mitochondrial abnormalities. Moreover, HgCl 2 exposure induced oxidative stress, characterized by a decrease in antioxidant capacity and an increase in lipid peroxidation. Further studies revealed increased total iron level and dysregulation of iron metabolism‐related proteins. It can be concluded that HgCl 2 exposure disrupted BBB integrity, promoted iron overload‐mediated oxidative stress, initiated ferroptosis, and ultimately exacerbated brain injury in embryos. These findings highlight the critical role of ferroptosis in HgCl 2 ‐induced neurotoxicity and offer novel mechanistic insights that may inform future strategies for preventing or treating heavy metal‐related neurological disorders.