Acupuncture regulates mitochondrial homeostasis in traumatic brain injury: current evidence, mechanistic hypotheses, and translational challenges

BACKGROUND: Traumatic brain injury (TBI) is associated with high morbidity, disability, and long-term neurological sequelae. Mitochondrial dysfunction is a central component of secondary injury after TBI, contributing to impaired energy metabolism, oxidative stress, calcium dysregulation, neuroinflammation, and neuronal apoptosis. MAIN BODY: This review summarizes current evidence regarding acupuncture-mediated regulation of mitochondrial homeostasis after TBI, focusing on structural homeostasis, quantitative homeostasis, and functional/metabolic homeostasis. We distinguish direct evidence from TBI models, indirect evidence from related brain injury models, and hypothesis-generating mechanisms. Particular attention is given to mitochondrial dynamics, mitochondrial biogenesis, mitophagy, energy metabolism, oxidative stress, calcium signaling, mitochondrial membrane potential, apoptosis, intercellular mitochondrial transfer, and putative upstream neural and humoral pathways. CONCLUSION: Current preclinical evidence suggests that acupuncture, particularly electroacupuncture, may influence mitochondrial homeostasis after TBI through multidimensional and context-dependent mechanisms. However, direct TBI-specific evidence remains limited, and several proposed mechanisms require further validation before acupuncture-mediated mitochondrial regulation can be considered a clinically established therapeutic strategy.