Traumatic brain injury (TBI) is a critical neurological condition, with neuronal damage being its fundamental pathological basis. However, molecular targets for the prevention and treatment of neuronal injury remain to be further explored. Parkin is an important molecule closely associated with neurodegenerative diseases, yet relatively few studies have investigated its relationship with TBI. In this study, we first established and validated both the controlled cortical impact (CCI) and traumatic neuronal injury (TNI) models. Using these models, we revealed that TBI led to the upregulation of Parkin expression, with a peak occurring 24 h post-injury. Furthermore, at the in vitro level, lentivirus-mediated modulation of Parkin expression revealed that Parkin overexpression alleviated TNI-induced neurotoxicity, apoptosis, oxidative stress, and mitochondrial dysfunction, whereas Parkin knockdown exacerbated neuronal damage. At the mechanistic level, the study demonstrated that Parkin promoted mitochondrial biogenesis and fission while inhibiting mitochondrial fusion and attenuated the impairment of mitophagy after TBI. In other words, Parkin exerts a neuroprotective role through regulating mitochondrial quality control. We further employed adeno-associated viruses and Parkin knockout mice to modulate Parkin expression in vivo. The results showed that Parkin attenuated CCI-induced brain damage, edema, and behavioral deficits, whereas Parkin knockout exacerbated brain injury and functional impairments. Finally, we designed and synthesized a recombinant Parkin protein and preliminarily validated its protective effects at the cellular level. In summary, this study provides new insights for the therapeutic targets against TBI.
Wu et al. (Sun,) studied this question.