Epigenetics in Traumatic Brain Injury

Following traumatic brain injury (TBI), changes in proteins, metabolites, and gene expression are highly dynamic and are influenced by genetic and environmental factors, circadian rhythms, and injury characteristics, including injury type (focal or diffuse), severity (mild to severe), and stage of recovery (acute, subacute, and chronic). These molecular alterations are accompanied by epigenetic modifications that regulate gene expression and contribute to injury progression and recovery. In this review, we integrate and summarize preclinical and clinical studies examining DNA methylation, histone methylation and acetylation, microRNA (miRNA)-mediated regulation, RNA epigenetic modifications, and mitochondrial epigenetic (mitoepigenetic) changes following TBI. Most studies have focused on DNA methylation, histone modifications, and miRNAs in experimental models, providing important insights into cell type-specific epigenetic responses after injury. We also review studies evaluating therapeutic strategies, including DNA methyltransferase and histone deacetylase inhibitors, that target epigenetic mechanisms to improve TBI outcomes.