Research progress on the relationship between mitochondrial dysfunction and inflammatory response in brain cells following traumatic brain injury: A review.

Traumatic brain injury (TBI) initiates a complex secondary injury cascade, within which the bidirectional crosstalk between mitochondrial dysfunction and neuroinflammation forms a self-amplifying vicious cycle, termed the "mitochondria-inflammation axis." This axis is increasingly recognized as a core mechanism driving progressive neural damage. Following TBI, impaired mitochondria not only cause bioenergetic failure but also release copious damage-associated molecular patterns (mtDNA, etc.) and reactive oxygen species (ROS), which potently activate innate immune platforms such as the NLRP3 inflammasome and NF-κB signaling. Conversely, the ensuing inflammatory milieu further aggravates mitochondrial damage through oxidative stress and disruption of quality control, creating a feed-forward loop. This review systematically synthesizes recent advances in understanding this axis, highlighting novel concepts like immunometabolic reprogramming of microglia and intercellular mitochondrial transfer. Furthermore, we critically evaluate emerging therapeutic strategies aimed at breaking this cycle, including mitochondria-targeted antioxidants, precise immunomodulators, and pioneering mitochondrial transplantation. By integrating evidence from multi-omics studies and diverse models, this review provides a unified conceptual framework for understanding TBI pathophysiology and illuminates promising avenues for future translational research.