Traumatic Brian Injury (TBI) unraveled: molecular disruptions and therapeutic avenues

Traumatic brain injury is a serious neurological disorder caused by external mechanical forces that disrupt brain structure and function. Approximately 25% of all injury-related deaths occur annually. The highest incidence is reported in adults aged 75 years and older (1682.0 per 100,000), followed by children aged 0–4 years and young adults aged 15–24 years. TBI pathophysiology involves an initial primary injury caused by direct mechanical impact, followed by a secondary injury phase marked by the progression of molecular and cellular disturbances. These include excitotoxicity, oxidative stress, mitochondrial dysfunction, ion imbalance, and neuroinflammation, which are driven by dysregulation of gene expression and signaling pathways. The resulting release of glutamate, reactive oxygen species, and inflammatory cytokines triggers apoptotic and necrotic cell death, leading to further neuronal loss. TBI is a non-focal disorder that targets multiple pathologies and symptoms at a single point in time. Thus, there are currently no available therapies to target brain injuries. Only therapies available target and provide symptomatic relief for the management of associated complications. Therefore, in this review, we provided a concise overview of the pathophysiology processes and molecular signaling pathways driving traumatic brain injury, while also exploring preclinical and current clinical strategies designed to counteract molecular dysfunction and promote neuroprotection.