ABSTRACT
Traumatic brain injury (TBI) is a major health and social problem in both developed and developing countries. In the US alone, an estimated 1.7 million civilians sustain TBI each year (Faul et al. 2010). Neurotrauma is most prevalent among young individuals, but with increased longevity of the general population, a high incidence of TBI is also observed in the elderly. The severity of TBI spans from mild TBI, which in the medical literature is often synonymous with concussion, to moderate and severe TBI. The morbidity and mortality in neurotrauma largely depend on the severity of secondary injury, which encompasses an array of pathophysiological processes, including the formation of cerebral edema, excitotoxicity, oxidative stress, and neuroinfl ammation. There has been signifi cant interest in both academia and industry in developing neuroprotective therapies for TBI, but many single-target neuroprotective interventions showing promising therapeutic potential in preclinical studies have failed to demonstrate consistent improvement of outcome in clinical trials (Tolias and Bullock 2004, Marklund et al. 2006, Wang et al. 2006, Schouten 2007). This may be, in part, due to the complex and interdependent nature of pathophysiological mechanisms
1 Neurotrauma and Brain Barriers Research Laboratory, Department of Emergency Medicine, Alpert Medical School of Brown University, Coro Center West, Room 112, 1 Hoppin Street, Providence, RI 02903, USA.
