IMR Press / FBL / Volume 29 / Issue 3 / DOI: 10.31083/j.fbl2903103
Open Access Review
Genetic Contributions to Recovery following Brain Trauma: A Narrative Review
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1 Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Champaign, IL 61801, USA
2 College of Engineering, Northeastern University, Boston, MA 02115, USA
3 Department of Neurosurgery, University of Florida, Gainesville, FL 32608, USA
*Correspondence: dlakshmipathy@gmail.com (Deepak Lakshmipathy)
Front. Biosci. (Landmark Ed) 2024, 29(3), 103; https://doi.org/10.31083/j.fbl2903103
Submitted: 9 November 2023 | Revised: 8 January 2024 | Accepted: 22 January 2024 | Published: 15 March 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Traumatic brain injury (TBI) is a frequently encountered form of injury that can have lifelong implications. Despite advances in prevention, diagnosis, monitoring, and treatment, the degree of recovery can vary widely between patients. Much of this is explained by differences in severity of impact and patient-specific comorbidities; however, even among nearly identical patients, stark disparities can arise. Researchers have looked to genetics in recent years as a means of explaining this phenomenon. It has been hypothesized that individual genetic factors can influence initial inflammatory responses, recovery mechanisms, and overall prognoses. In this review, we focus on cytokine polymorphisms, mitochondrial DNA (mtDNA) haplotypes, immune cells, and gene therapy given their associated influx of novel research and magnitude of potential. This discussion is prefaced by a thorough background on TBI pathophysiology to better understand where each mechanism fits within the disease process. Cytokine polymorphisms causing unfavorable regulation of genes encoding IL-1β, IL-RA, and TNF-α have been linked to poor TBI outcomes like disability and death. mtDNA haplotype H has been correlated with deleterious effects on TBI recovery time, whereas haplotypes K, T, and J have been depicted as protective with faster recovery times. Immune cell genetics such as microglial differentially expressed genes (DEGs), monocyte receptor genes, and regulatory factors can be both detrimental and beneficial to TBI recovery. Gene therapy in the form of gene modification, inactivation, and editing show promise in improving post-TBI memory, cognition, and neuromotor function. Limitations of this study include a large proportion of cited literature being focused on pre-clinical murine models. Nevertheless, favorable evidence on the role of genetics in TBI recovery continues to grow. We aim for this work to inform interested parties on the current landscape of research, highlight promising targets for gene therapy, and galvanize translation of findings into clinical trials.

Keywords
traumatic brain injury
recovery genetics
pathophysiology
cytokine polymorphism
mitochondrial DNA
gene therapy
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