Ferroptosis-relevant mechanisms and biomarkers for therapeutic interventions in traumatic brain injury

Traumatic brain injury (TBI) is one of the most significant health care problems worldwide, causing disability and death especially among young individuals. Although a large range of agents and therapies have been proved beneficial to lesions post-TBI to some extent, effective treatments have not been translated to the clinic. As a newly discovered form of iron-dependent regulated cell death, ferroptosis has been implicated in TBI. In this review, we update the current state of knowledge related to second injuries post-TBI, including ferroptosis, oxidative stress, mitochondrial dysfunction, neuroinflammation and so on, which often lead to chronic symptoms and long-term disability. This review systematically summarizes the latest progress in the pathophysiological mechanisms of TBI, with a focus on providing references for proposing new multi-molecular targets for comprehensive therapeutic strategies based on ferroptosis-relevant mechanisms. In addition, biomarkers are essential diagnostic and prognostic tools in TBI. Several biomarkers associated with the outcome of TBI have been listed in this article, such as Pde10a, MDA, UCH-L1, S100A9, S100B, ALDOC, ACSL4, MBP and F2-Isoprostane. Therefore, the understating of ferroptosis-relevant mechanisms and biomarkers may contribute to development of promising therapies for TBI clinical trials.