Traumatic brain injury (TBI) can have various harmful long-term neurological effects, including problems with vision, coordination, memory, mood, and thinking. According to the Centers for Disease Control and Prevention, traumatic brain injury from a head injury is a leading cause of death and disability in the United States, and close to 5 million Americans—soldiers and non-soldiers alike—are currently living with a traumatic brain injury related disability. Current therapy for these patients involves supportive care and rehabilitation, but no treatments are available that can prevent the development of chronic neurological symptoms.
Researchers from the University of Iowa believe they may have identified a potential approach for preventing the development of neurological problems associated with traumatic brain injury . Their research in mice suggests that protecting axons—the fiber-like projections that connect brain cells—prevents the long-term neuropsychiatric problems caused by blast-related traumatic brain injury.
In a recent study, the UI team led by Andrew Pieper, professor of psychiatry at the UI Carver College of Medicine, investigated whether early damage to axons—an event that is strongly associated with many forms of brain injury, including blast-related traumatic brain injury —is simply a consequence of the injury or whether it is a driving cause of the subsequent neurological and psychiatric symptoms.
To answer that question, the researchers used mice with a genetic mutation that protects axons from some forms of damage. The mutation works by maintaining normal levels of an important energy metabolite known as nicotinamide adenine dinucleotide (NAD) in brain cells after injury. When mice with the mutation experienced blast-mediated traumatic brain injury , their axons were protected from damage, and they did not develop the vision problems, or the thinking and movement difficulties that were seen when mice without the mutation experienced blast-related traumatic brain injury . The findings were published Oct. 11 in the online journal eNeuro.
“Our work strongly suggests that early axonal injury appears to be a critical driver of neurobehavioral complications after blast traumatic brain injury ,” says Pieper, who also is a professor of neurology, radiation oncology, and a physician with the Iowa City Veterans Affairs Health Care System. “Therefore, future therapeutic strategies targeted specifically at protecting or augmenting the health of axons may provide a uniquely beneficial approach for preventing these patients from developing neurologic symptoms after blast exposure.”
In confirming the critical relationship between axon degeneration and development of subsequent neurological complication, the new study builds on previous work from Pieper’s lab. The researchers also have discovered a series of neuroprotective compounds that appear to help axons survive the kind of early damage seen in TBI. These compounds activate a molecular pathway that preserves neuronal levels of NAD, the energy metabolite that has been shown to be critical to the health of axons. Pieper’s team previously demonstrated that these neuroprotective compounds block axonal degeneration and protect mice from harmful neurological effects of blast traumatic brain injury , even when the compound are given 24 to 36 hours after the blast injury.
Citation: Acute axonal degeneration drives development of cognitive, motor and visual deficits after blast-mediated traumatic brain injury in mice. Authors: Terry C. Yin, Jaymie R. Voorhees, Rachel M. Genova, Kevin Davis, Ashley Madison, Jeremiah K. Britt, Coral J. Cintrón-Pérez, Latisha McDaniel, Matthew M. Harper, Andrew A. Pieper
Research funding: Calico LLC (California Life Company), Mary Alice Smith Fund for Neuropsychiatry Research
Adapted from press release by The University of Iowa
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