Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy

Abstract

Traumatic brain injury (TBI) contributes to nearly a third of all injury-related deaths in the United States. For survivors of TBI, depending on severity, patients can be left with devastating neurological disabilities that include impaired cognition or memory, movement, sensation, or emotional function. Despite the efforts to identify novel therapeutics, the only strategy to combat TBI is risk reduction (helmets, seatbelts, removal of fall hazards, etc.). Enormous heterogeneity exists within TBI, and it depends on the severity, the location, and whether the injury was focal or diffuse. Evidence from recent studies support the involvement of epigenetic mechanisms such as DNA methylation, chromatin post-translational modification, and miRNA regulation of gene expression in the post-injured brain. In this review, we discuss studies that have assessed epigenetic changes and mechanisms following TBI, how epigenetic changes might not only be limited to the nucleus but also impact the mitochondria, and the implications of these changes with regard to TBI recovery.

Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury

“…The genomic response to injury is an important area of current research. Recent studies have revealed that traumatic injuries result in epigenetic changes via DNA methylation, phosphorylation, and acetylation (Wong & Langley, 2016). The so-called "genomic storm" following injury occurs on an epigenetic level and modulates numerous cellular functions, protein expression, and pathways.…”

The ‘Omics’ of Epigenetic Modulation by Valproic Acid Treatment in Traumatic Brain Injury—What We Know and What the Future Holds

“…These changes are collectively referred to as “epigenetics” and involve modulation of gene expression and phenotype while maintaining the underlying DNA sequence. Of note, these epigenetic changes following TBI have also been implicated in recovery from TBI as well . Therefore, modulation of these pathways can may play a potential role in treatment of TBI.…”

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

“…Overall, these studies have shown a potential role of miRNA as TBI biomarkers, but only miR21 has been identified as a candidate in more than one study [198,199]. Given that pre-clinical optimism in finding good biomarkers in the past has not been successfully translated in clinical settings [200], further evaluation of these miRNAs with larger, multicenter patient cohorts is needed to explore their use as effective biomarkers applied to diagnosis and prognosis of TBI.…”