Navneet Singh

Traumatic Brain Injury (TBI) is a major global health concern and a leading cause of mortality and long-term disability. Alongside the primary brain injury, patients often experience secondary complications, including TBI-induced coagulopathy, neurovascular dysfunction, and systemic inflammation. Recent studies highlight mitochondrial dysfunction as a pivotal factor confounding these pathophysiological responses. Platelets, critical components of the haemostatic system, undergo mitochondrial dysfunction following TBI, contributing directly to coagulation imbalance and poor clinical outcomes. Concurrently, studies have reported elevated levels of circulating cell-free DNA (ccfDNA), including mitochondrial DNA (mtDNA), in TBI patients. These fragments act as potent Damage-Associated Molecular Patterns (DAMPs), activating innate immune receptors such as the STING (Stimulator of Interferon Genes) pathway, which further amplifies inflammation and tissue injury. The combined effect of mitochondrial dysfunction, platelet impairment, and STING-driven immune activation further intensify the secondary injury cascade leading to poor outcome in TBI patients. Investigating these mechanisms offers a promising avenue for the development of early diagnostic biomarkers and targeted therapeutic strategies. A deeper understanding of circulating mitochondrial biomarkers and their role in TBI-induced systemic complications could pave the way for more effective clinical interventions, ultimately improving prognosis, accelerating recovery, and enhancing the quality of life for TBI patients.