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Published Online: 29 September 2022

Epigenetic Modifications and Their Potential Contribution to Traumatic Brain Injury Pathobiology and Outcome

Publication: Journal of Neurotrauma
Volume 39, Issue Number 19-20


Epigenetic information is not permanently encoded in the DNA sequence, but rather consists of reversible, heritable modifications that regulate the gene expression profile of a cell. Epigenetic modifications can result in cellular changes that can be long lasting and include DNA methylation, histone methylation, histone acetylation, and RNA methylation. As epigenetic modifications are reversible, the enzymes that add (epigenetic writers), the proteins that decode (epigenetic readers), and the enzymes that remove (epigenetic erasers) these modifications can be targeted to alter cellular function and disease biology. While epigenetic modifications and their contributions are intense topics of current research in the context of a number of diseases, including cancer, inflammatory diseases, and Alzheimer disease, the study of epigenetics in the context of traumatic brain injury (TBI) is in its infancy. In this review, we will summarize the experimental and clinical findings demonstrating that TBI triggers epigenetic modifications, with a focus on changes in DNA methylation, histone methylation, and the translational utility of the universal methyl donor S-adenosylmethionine (SAM). Finally, we will review the evidence for using methyl donors as possible treatments for TBI-associated pathology and outcome.

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Published In

cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 39Issue Number 19-20October 2022
Pages: 1279 - 1288
PubMed: 35481812


Published in print: October 2022
Published online: 29 September 2022
Published ahead of print: 14 June 2022
Published ahead of production: 28 April 2022


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Laura Zima
Department of Neurological Surgery, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
Rebecca West
Department of Neurobiology and Anatomy, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
Paul Smolen
Department of Neurobiology and Anatomy, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
Nobuhide Kobori
Department of Neurobiology and Anatomy, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
Georgene Hergenroeder
Department of Neurological Surgery, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
HuiMahn A. Choi
Department of Neurological Surgery, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
Anthony N. Moore
Department of Neurobiology and Anatomy, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
John B. Redell**
Department of Neurobiology and Anatomy, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.
Pramod K. Dash**,* [email protected]
Department of Neurobiology and Anatomy, University of Texas Health Science Center McGovern Medical School, Houston, Texas, USA.


Co-senior authors.
Address correspondence to: Pramod Dash, PhD, Department of Neurobiology and Anatomy, UTHealth McGovern Medical School, 6431 Fannin Street, MSB 7.046, Houston, TX 77030, USA [email protected]

Authors' Contributions

LZ, RW, PS, NK, GH, HAC, ANM, JBR, and PKD all contributed to the review of relevant literature, writing, and/or editing of the article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

Research in authors' laboratories is supported by grants from the National Institutes of Health (R01NS118329, R01NS101686, R01NS121261, and R01NS109118).

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