Pathophysiology of severe traumatic brain injury

Traumatic brain injury is a leading cause of morbidity and mortality globally, particularly among young people, with significant social and economic effects. The World Health Organization (WHO) estimates that more than five million people die each year from traumatic injuries worldwide. While public health initiatives such as seatbelts and airbags have had a major impact, it will be impossible to prevent traumatic brain injury. Therefore, it is important that we understand the pathophysiology of secondary brain injury to be able to effectively treat our patient and also to develop novel targets of future interventions. The mechanisms of secondary brain injury are complex involving alterations in cerebral perfusion, activation of inflammatory cytokines and excitotoxicity. While our understanding of these mechanisms has advanced greatly over the last decade, there is still much to learn and great uncertainty at the bedside. There has been some recent success with the discovery of some simple interventions that can reduce secondary brain injury and improve outcomes in patients after traumatic brain injury. In this review we summarize the current understanding of mechanisms and pathophysiology of primary and secondary brain injury, the goals for current treatment and potential targets for future therapy.