Neuroscience Research Explores Traumatic Brain Injury

• RSS
• Print

Alan I. Faden, MD, professor of neuroscience, likes to question common beliefs, taking on such eclectic issues as physician error, religious differences in bioethics, or concepts about neurotrauma.

Perhaps his iconoclastic views reflect his unusual training - which includes an undergraduate degree in physics, graduate work in philosophy of science, medical training, and neurology specialization. Or it may reflect his diverse professional experience: emergency medicine, military medicine, academic neurology, institute director, research dean, and leadership of three medical societies.

The fact that medical error resulted in the death of his father led Faden to co-author a book, Medical Harm, in 1998, on physician-caused illness – one of the first to critically address both the problem and potential fixes. He has also published in bioethics and co-edited another book comparing bioethics perspectives between Jewish and Catholic traditions.

But brain and spinal cord injury are where he has most challenged traditional concepts. When he began his research, classical clinical belief held that trauma caused immediate, irreversible tissue damage. Faden was among a few scientists who then believed that much of the damage resulted from delayed biochemical changes that could be modified. His laboratory subsequently identified a number of important secondary injury factors, which has led to development of novel protective compounds - one of which is currently being developed for treatment of head injury. It is an example of a multi-potential drug, a concept initially proposed by Faden in the early 1980’s which favors use of relatively “dirty drugs” that hit multiple therapeutic targets. This view, a distinct contrast to the focus of most pharmaceutical companies, has recently gained acceptance in trauma circles, he says.

Yet Faden is most excited by new data that further challenge traditional views of injury and treatment. The lesion core produced after trauma is considered untreatable, because it reflects necrotic cell death that is completed within hours. But Faden’s group has shown that a less well-studied form of programmed cell death is prevalent in the core and can be blocked many hours or perhaps even days after injury- resulting in dramatically improved recovery.

Perhaps even more threatening to traditional views, he says, is his lab’s recent discovery of a cluster of “inflammatory” genes that is expressed late after trauma and may continue to damage tissue indefinitely if not turned off. Because progressive loss of brain tissue after trauma can continue for years, it may be possible to target these inflammatory pathways long after injury and still improve recovery. He adds that these findings may also help to explain how head injury can increase the probability of developing Alzheimer’s or Parkinson’s disease decades later.

“What is remarkable,” Faden says, “is that it might be possible to reduce progressive damage from head or spinal cord injury, even if treatment begins months after trauma, or to limit the development of subsequent chronic neurodegenerative diseases.”

By Renee Twombly, GUMC Communications