From oxidative stress to epigenetic regulation: Molecular mechanisms of preterm brain injury and neuroprotective strategies (Review).

Preterm brain injury remains a leading cause of long‑term neurodevelopmental impairment despite advances in neonatal care. Oxidative stress (OS), arising from mitochondrial dysfunction, nicotinamide adenine dinucleotide phosphate oxidase activation and iron‑mediated Fenton reactions, selectively damages the developing brain because of immature antioxidant defenses and vulnerable oligodendrocyte progenitor cells. Critically, OS triggers enduring epigenetic modifications including DNA methylation alterations, histone acetylation changes and microRNA dysregulation, thereby translating acute perinatal insults into sustained changes in gene expression. The complex cellular interplay involving microglia, astrocytes and the neurovascular unit determines injury progression and repair capacity. Emerging neuroprotective strategies include antioxidant therapies, pathway‑targeted agents and cell‑based approaches, while artificial intelligence applications show promise for early risk stratification and personalized monitoring, although these tools remain under prospective validation. The present review synthesized current evidence on the pathological cascade from OS to epigenetic dysregulation in preterm brain injury, evaluated the latest advances in neuroprotective interventions and aimed to inform the development of precision‑based, developmentally timed interventions that address the multifactorial nature of preterm brain injury and improve long‑term neurodevelopmental outcomes.