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

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.