The clinical understanding of traumatic brain injury (TBI) and its manifestations is beginning to change. Both clinicians and research scientists are recognizing that TBI and related disorders such as stroke are complex, systemic inflammatory and degenerative diseases that require an approach to treatment more sophisticated than targeting a single gene, receptor, or signaling pathway. It is becoming increasingly clear that TBI is a form of degenerative disorder affecting the brain and other organs, and that its manifestations can unfold days, weeks, and years after the initial damage. Until recently, and despite numerous industry- and government-sponsored clinical trials, attempts to find a safe and effective neuroprotective agent have all failed - probably because the research and development strategies have been based on an outdated early 20th century paradigm seeking a magic bullet that will affect a narrowly circumscribed target. We propose that more attention be given to the development of drugs, given alone or in combination, that are pleiotropic in their actions and that have systemic as well as central nervous system effects. We review current Phase II and Phase III trials for acute pharmacologic treatments for TBI and report on their aims, methods, status, and important associated research issues.
Keywords: Neuroprotectant; antioxidant; coagulopathy; glutamate antagonist; immunomodulator; pharmacology; steroid.
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