By Kasra Zarei
The brain is arguably the most important organ in the human body — it controls actions and defines humanity. Unlike a normal limb injury, then, a brain injury can directly alter many aspects of an individual’s life, including personality.
According to the Centers for Disease Control & Prevention, approximately 1.5 million people in the United States suffer from traumatic brain injury every year, which causes long-term disabilities and deaths.
It can be caused by a variety of means, including head-impact injury or an explosion, which is called blast-associated traumatic brain injury. Each form of injury carries its own characteristic set of consequences.
Blast-associated injuries have become the signature injury for U.S. soldiers serving in the Middle East, creating a great need for targeted therapies.
Andrew Pieper, a UI professor of psychiatry, led a new study in mice that has shown early damage to axons — the long, tendril-like connections between neurons that make brain-cell communication possible — to be the key to the development of the subsequent long-term neurological complications that develop after blast injury.
“Before [the experiment] we knew that axons degenerated, but it was unknown whether this degeneration was a determinative critical step in blast-associated [injury] or a consequence of the broader picture of injury,” Pieper said.
Axonal damage has long been associated with blast-associated injury, but its specific role as a driving force or a general consequence of damage has been unknown.
Pieper and his team used an established model of mice that carry a genetic mutation and is resistant to some forms of axonal degeneration.
“We had a model in place — we wanted to answer whether specifically blocking axonal injury would reduce the broad spectrum of functional deficits that normal mice experience after blast injury,” Pieper said.
The study showed that mice with axonal injury blocked do not develop the expected neurological deficits that genetically normal mice experience.
Pieper’s team, including Terry Yin, a UI postdoctoral research scholar and first author on the study, looked at neurological deficits from several angles, including motor coordination, learning and memory, and visual function. Unlike the genetically normal mice, the mutant mice resistant to axonal degeneration maintained function in all categories.
The study demonstrated that axonal degeneration is a critical early event in blast-associated injury. Thus, therapies targeted at preventing or mitigating early axonal degeneration may provide a beneficial approach for treating those affected.
“We have confirmation of the fact that axonal degeneration is crucial in this mechanism and driving neurobehavioral complications after blast-injury,” Pieper said. “Therefore, treatments aimed at preserving axons are worthwhile to further explore as possible new ways to treat patients suffering from this condition.”
The study also provides a unique opportunity to vet potential pharmacological treatments that may prove valuable for treating blast-associated injury.
“We are able to model blast injury in a pre-clinical setting, which allows us to test candidate therapeutics for drug treatment,” Yin said.
Andrew Peterson, a UI clinical associate professor of orthopedics and pediatrics, noted the importance of research surrounding axonal degeneration.
“Preventing axonal degeneration has been a target of research — if you can keep brain cells functioning, then it would be good for recovery from brain injury,” Peterson said.
