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Every year traumatic brain injury (TBI) causes 50,000 deaths and 80,000 cases of long-term disability in the United States, according to the Centers for Disease Control and Prevention. An estimated 5.3 million Americans (some 2 percent of the population) live with long-term disabilities due to brain injury.

Yet much about brain injuries remains unknown. Despite decades of research, no treatments yet target the underlying pathophysio­logical cause of progressive brain damage. For patients so severely injured that they are in a minimally conscious state, medical knowledge is particularly lacking; in such cases, we are just beginning to understand the damage and the possibility of treatment (see “Raising Consciousness”).

Preventing brain injuries is enormously important. Prevention strategies include such commonsense devices as air bags in cars, protective helmets, and cushioned playground materials. Detailed knowledge of TBI biomechanics at both the whole-body and single-cell levels can make prevention even more successful. Equipped with this information, computational models can predict how likely an event is to cause injury and how effective a protective device is likely to be.

Finding treatments for those injuries that do occur will depend on better understanding the complex cellular events triggered by a brain injury. In TBI, a rapid mechanical deformation of the brain both physically disrupts and mechanically stimulates cells. Some cell damage is immediate, but most of the damage develops over days, weeks, and even months. The delayed and progressive nature of the neurodegenerative cascade represents a critical therapeutic opportunity: targeted intervention could halt the progression of cell damage and death. However, no therapeutic strategies yet exist that target the degeneration mechanisms.

One approach, which my research group is working on, is to develop experimental TBI models that simulate the neurodegenerative sequence. With the molecular understanding that such models offer, promising therapeutic targets can be identified and treatments rationally developed with the intent of breaking the progression from mechanical event to delayed cell death. Boosting the brain’s own protective mechanisms is another possible tactic. Finally, therapeutic strategies to encourage sprouting of new brain tissue or regeneration of damaged tissue could also hold promise for those living with long-term disability.

Our understanding of TBI is greater today than it has ever been. But TBI must continue to be studied so that effective treatments can be found for the approximately 230,000 people each year who suffer head injuries that require hospitalization.

Barclay Morrison is an assistant professor of biomedical engineering at Columbia University and the principal investigator in its Neuro­trauma and Repair Laboratory.

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Credit: Illustration by Marc Rosenthal

Tagged: Biomedicine

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