Epigenetic mechanisms in post-stroke neuronal resilience and survival pathways

Ischemic stroke is a leading cause of permanent neurological disability worldwide, primarily driven by neuronal injury mechanisms such as excitotoxicity and oxidative stress. Consequently, understanding the molecular basis of post-ischemic neural repair has emerged as a critical focus in translational neuroscience. Accumulating evidence now points to a central orchestrator in this repair process: dynamic epigenetic regulation. This regulation, which encompasses mechanisms like DNA methylation/demethylation, histone modifications, non-coding RNA networks, and chromatin remodeling, modulates key repair pathways including neuroinflammation, axonal regeneration, and synaptic plasticity. In this context, the present review synthesizes current evidence on two fronts: first, how these epigenetic mechanisms regulate neuroinflammation and oxidative stress; and second, their specific roles in promoting neurogenesis and neuroplasticity after stroke. By integrating these insights, this review aims to provide a coherent theoretical foundation for the rational development of epigenetic-targeted therapeutic strategies to enhance functional recovery following stroke.