Epigenetic reprogramming in traumatic brain injury

Traumatic brain injury (TBI) initiates a cascade of secondary molecular and cellular events that drive long-term neurological dysfunction. Increasing evidence positions epigenetic regulation as a central integrative mechanism through which acute injury-related signals are translated into sustained alterations in gene expression, cell state, and circuit function. Epigenetic mechanisms—including DNA methylation, histone modifications, and non-coding RNAs—act in a coordinated, cell type–specific manner to shape transcriptional programs underlying neuroinflammation, synaptic remodeling, and behavioral outcomes after TBI. Recent advances in epigenomic and transcriptomic profiling, particularly single-cell, spatial, and integrative multi-omics approaches, have enabled systems-level interrogation of injury-induced regulatory networks across neurons, glia, and the neurovascular unit. Beyond mechanistic insight, epigenetic reprogramming provides a conceptual framework for biomarker discovery and therapeutic development, given the accessibility and reversibility of epigenetic states. This review synthesizes current evidence to highlight how epigenetic mechanisms link acute brain injury to chronic neurological sequelae and discusses emerging opportunities for epigenetically informed precision medicine in TBI.