Each year in the United States alone, a third of a million persons are hospitalized for traumatic brain injury (TBI), of whom approximately 1/4 die. Most are less than 30 years of age. Not only are the health care costs staggering for both initial care and rehabilitation, but the societal loss in terms of economic impact reaches into the billions of dollars annually in the U.S. alone. Despite advances in neurosurgical interventions and intensive care management, many survivors do not fully recover. A significant cause of this mortality and morbidity is thought due to potentially preventable secondary injury, namely oxidant injury, inflammation, and apoptosis in the penumbra (the area of brain surrounding the primary lesion, which is at-risk, but potentially salvageable), beginning in the first few hours after the severe traumatic event.

Despite the current bleak outlook for many of these patients, a series of animal investigations have uncovered a promising solution to the problem of the secondary injury seen in severe TBI and other similar processes, namely the early administration of estrogen, a strong anti-oxidant, anti-inflammatory and anti-apoptotic compound. Based on these encouraging results from animal studies, the investigators hypothesize that early administration of IV Premarin® in patients with severe TBI will safely reduce secondary brain injury, improve neurological outcomes, and improve survival.