Work

Mitochondrial metabolic remodeling and blood–brain barrier dysfunction after repetitive mild traumatic brain injury

Year: 2026

Type: review

Abstract: Repetitive mild traumatic brain injury (rmTBI) may arise when concussive or subconcussive impacts recur before physiological recovery is complete. Mitochondrial dysfunction and blood-brain barrier (BBB) impairment are shared features across the traumatic brain injury (TBI) spectrum; in rmTBI, repetition may alter their magnitude, duration, and temporal coupling. This focused narrative review evaluates evidence that mitochondrial metabolic remodeling contributes to neurovascular-unit dysfunction after rmTBI. We discuss energy failure, mitochondrial reactive oxygen species, succinate, fumarate, alpha-ketoglutarate, NAD + depletion, and lactate as candidate links between metabolic stress and BBB injury. Direct rmTBI evidence is prioritized, while single-TBI studies are used as mechanistic context when rmTBI data are limited. Available studies support a model in which recurrent metabolic stress, redox imbalance, inflammatory signaling, and impaired mitochondrial quality control converge on endothelial and multicellular neurovascular-unit dysfunction. Metabolism-directed interventions are promising but require validation across rigorously defined rmTBI paradigms and clinical cohorts.

Source: Frontiers in Molecular Neuroscience

DOI: 10.3389/fnmol.2026.1852115

Authors: Lingjuan Gao, Xincheng Xue, Xianhui Deng, Yu Xu, Heng Gao

Institutions: Xuzhou Medical College, Jiangyin People's Hospital

Language: English

Topic: Traumatic Brain Injury Research

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801