Mitochondrial Dysfunction in Traumatic Brain Injury and Its Theranostic Implications

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Traumatic brain injury (TBI) is a significant cause of neurological disability and death.
• Mitochondria are crucial organelles involved in neuronal metabolism, oxidative balance, and cell survival, making them key targets after TBI.

Purpose of the Study:

• To review the literature on mitochondrial dysfunction following TBI.
• To explore the role of mitochondria in TBI diagnosis, monitoring, prognostication, and treatment.

Main Methods:

• A narrative literature review was conducted.
• 159 references published between 1997 and 2026 were synthesized, with a focus on recent research (70 from 2020 onwards).
• The review followed SANRA guidelines.

Main Results:

• Mitochondrial dysfunction causes bioenergetic failure via impaired oxidative phosphorylation, altered reactive oxygen species (ROS) production, and calcium handling.
• Downstream effects include oxidative damage, epigenetic/proteomic changes, and programmed cell death (apoptosis, necroptosis, ferroptosis) within an inflammatory environment.
• Mitochondrial DNA and microRNA are potential biomarkers for TBI severity and prognosis.
• Investigational therapies include targeting the mitochondrial permeability transition pore, antioxidants, restoring NAD+-dependent pathways, and ketogenic interventions.

Conclusions:

• Advances in mitochondrial biology enhance understanding of TBI.
• Mitochondrial research provides a promising framework for improving TBI management.