Mitochondria: The Hidden Engines of Traumatic Brain Injury-Driven Neurodegeneration

 Has your competent? doctor done ANYTHING AT ALL with this earlier research on mitochondria? NO? so, you DON'T have a functioning stroke doctor, do you? How incompetent can your doctor be and still have a job? Serious question! Ask your hospital president that!

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Mitochondria: The Hidden Engines of Traumatic Brain Injury-Driven Neurodegeneration

Olusola A Olatona¹Sydney P Sterben¹Sahan B S Kansakar¹Aviva Jane Symes^2*Volha Liaudanskaya^1,3*

• ¹Biomedical Engineering, University of Cincinnati, Cincinnati, United States
• ²Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States
• ³Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States

The final, formatted version of the article will be published soon.

Mitochondria play a critical role in brain energy metabolism, cellular signaling, and homeostasis, making their dysfunction a key driver of secondary injury progression in traumatic brain injury (TBI). This review explores the relationship between mitochondrial bioenergetics, metabolism, oxidative stress, and neuroinflammation in the post-TBI brain. Mitochondrial dysfunction disrupts adenosine triphosphate (ATP) production, exacerbates calcium dysregulation, and generates reactive oxygen species, triggering a cascade of neuronal damage and neurodegenerative processes. Moreover, damaged mitochondria release damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA), Cytochrome C, and ATP, triggering inflammatory pathways that amplify tissue injury. We discuss the metabolic shifts that occur post-TBI, including the transition from oxidative phosphorylation to glycolysis and the consequences of metabolic inflexibility. Potential therapeutic interventions targeting mitochondrial dynamics, bioenergetic support, and inflammation modulation are explored, highlighting emerging strategies such as mitochondrial-targeted antioxidants, metabolic substrate supplementation, and pharmacological regulators of mitochondrial permeability transition pores. Understanding these mechanisms is crucial for developing novel therapeutic approaches to mitigate neurodegeneration and enhance recovery following brain trauma.

Keywords: Brain Injury, Mitochondria, neurodegeneration, Metabolism, Bioenergetics

Received: 03 Feb 2025; Accepted: 15 Apr 2025.

Copyright: © 2025 Olatona, Sterben, Kansakar, Symes and Liaudanskaya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.