Copper and cuproptosis-related genes as indictors for the diagnosis of injury time in traumatic brain injury: human cases and animal experiment

Traumatic brain injury (TBI) is one of the most frequently encountered injuries in forensic practice. Nevertheless, a major technical bottleneck persists: there are no stable, specific indicators available for estimating the injury time of TBI in either clinical or forensic settings, which severely hinders the efficiency and accuracy of relevant case identification. Against this backdrop, the present study centers on the spatiotemporal distribution of copper ions (Cu 2+ ) and the newly identified cuproptosis pathway, systematically investigating their associations with TBI progression via retrospective detection of human postmortem samples and prospective experiments on mouse TBI models. Preliminary findings revealed that within 30 days after TBI onset in humans, the copper content in the cerebral contusion area rises remarkably in a time-dependent manner, particularly in frozen-preserved cadaver samples. Concurrently, activation of the cuproptosis process was observed in the cerebral contusion region of mouse TBI models. Collectively, these findings may shed new light on the development of potential biomarkers for TBI injury time estimation. In addition, the expression levels of FDX1, DLD and SLC31A1 are applicable for inferring the time of early-stage TBI, while those of LIAS and SLC31A1 can facilitate the determination of injury time in late-stage TBI.