Mitochondrial Dysfunction in Traumatic Brain Injury and Its Theranostic Implications

Journal article : Review

Background: Traumatic brain injury (TBI) remains a major cause of neurological morbidity and mortality. Mitochondria, being embedded as one of the key organelles disrupted after injury, play a central role in regulating neuronal metabolism, oxidative balance, and cell survival, hence the growing interest in their role after TBI. Methods: We present a narrative review of the literature on mitochondrial dysfunction after TBI to highlight the potential role in diagnosis, monitoring, prognostication and treatment strategies. Following SANRA guidelines we conducted a synthesis of 159 selected references published between 1997 and 2026, including 70 references published from 2020 onward. Results: Mitochondrial dysfunction underpins bioenergetic failure through the impairment of critical regulatory pathways, including oxidative phosphorylation, dysregulated reactive oxygen species production, and dysregulated calcium handling. These changes trigger downstream processes of oxidative damage, epigenetic and proteomic remodeling, and activation of regulated cell death pathways such as apoptosis, necroptosis, and ferroptosis in the context of an inflammatory milieu. As such, mitochondrial-derived molecules (such as mitochondrial DNA and microRNA) are emerging candidate biomarkers of TBI severity and prognosis. Additionally, therapeutic approaches under investigation include inhibition of the mitochondrial permeability transition pore, mitigation of mitochondrial oxidative stress using targeted antioxidants, restoration of NAD+-dependent metabolic pathways, and metabolic support through ketogenic interventions. Conclusions: Mitochondrial biology is advancing our understanding of TBI and offers a promising framework for improving its management.

Authors: Himic, V; Tchantchaleishvili, N; Netliukh, A; Chibbaro, S; Syrmos, N

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: Biomolecules
• Volume: 16
• Issue: 6
• Pages: 762
• Article number: 762
• Publication date: 2026-05-22
• Acceptance date: 2026-05-18
• DOI: 10.3390/biom16060762
• EISSN: 2218-273X
• ISSN: 2218-273X
• Language: English
• Keywords: traumatic brain injury; neuroenergetics; mitochondrial dysfunction; theranostics; neuro-critical care; oxidative stress; neurosurgery
• Subtype: Review