Altered iron homeostasis in neonatal hypoxic-ischemic encephalopathy

Abstract

Hypoxic-ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and long-term neurological impairment, even with therapeutic hypothermia as the current standard of care. Emerging evidence suggests that disrupted iron homeostasis-characterized by labile iron overload, ferritin degradation, and accumulation of cell-free hemoglobin-may exacerbate secondary brain injury through oxidative stress, neuroinflammation, and ferroptosis. Neonatal vulnerability is heightened by immature antioxidant systems and the unique biochemical properties of fetal hemoglobin. We hypothesize that these iron-mediated pathways are central to the progression of neuronal injury in neonatal HIE. Targeting iron dysregulation, including the use of iron chelators and ferroptosis inhibitors, could offer a novel adjunctive strategy to improve neuroprotection in affected neonates. This conceptual framework invites further experimental and translational studies to validate iron homeostasis as a therapeutic target in neonatal brain injury.