Traumatic brain injury and molecular biology: A new narrative

Annually, traumatic brain injury affects over 50 million people worldwide. Disability and death arise from both primary mechanical injury and secondary molecular mechanisms. Within 24h of injury, intracranial neuroinflammatory processes are triggered. Traumatic brain injury also initiates glutamate excitotoxicity, imbalance in calcium homeostasis, nitric oxide release from post-synaptic neurons, and Na +-K +-2Cl- co-transporters activation. This causes neuronal damage and consequential cognitive deterioration. Additionally, lipid oxidation causes mitochondrial damage, producing reactive oxygen species. These downstream pathways are inter-linked and result in irreversible damage through neuronal cell necrosis, apoptosis, necroptosis, and autophagy. Prolonged activation of these cascades contributes to development of long-term sequelae post-traumatic brain injury including post-traumatic epilepsy, depression, chronic traumatic encephalopathy, and Parkinson’s disease. Preclinical and clinical trials are investigating the role of various TBI diagnostic markers like S100β, glial fibrillary acidic protein, and ubiquitin carboxy-terminal hydrolase L1. Therapeutic agents targeting neuroinflammation, mitochondrial dysfunction, and excitotoxicity show promise in treating traumatic brain injury complications.