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While the brain’s immune system is vital to brain health, it can also become active in ways that damage the brain. Through brain imaging and blood sampling from active-duty and retired service members who are repeatedly exposed to blasts in training and operations, researchers in one component of the project will seek to better understand how the immune system may be contributing to brain inflammation and TBI.

“I am excited to be part of this team effort to develop the knowledge needed to protect the brains of service members against the effects of repeated low-level blast exposures,” said Dr. James Stone, a University of Virginia School of Medicine radiologist. “Using advanced brain imaging to directly visualize inflammation along with blood sampling, we hope to develop a better understanding of how the brain and immune system react to blast exposures.”

While most service members recover from TBI within weeks, about a third will have long-term symptoms. The project’s second component will seek to identify inflammatory markers in the brain that are connected to longer recovery periods from a TBI, which could help identify service members at higher risk for poor outcomes after a brain injury, as well as identify potential treatment options.

According to the Centers for Disease Control and Prevention, more than 430,000 service members were diagnosed with a TBI from 2000 to 2020. A TBI can cause mild symptoms like dizziness and confusion, or more debilitating symptoms including behavior and mood changes.

“Our new laboratory methods related to brain-derived exosomes provide a unique opportunity to understand pathological changes that may relate to the chronic symptoms observed in military personnel and veterans. Combining this with the novel imaging methods will greatly advance our understanding of blast exposures,” said Jessica Gill, a Johns Hopkins School of Nursing researcher.

In the project’s third component, researchers will use brain imaging and blood sampling from veterans diagnosed with chronic TBI to determine whether their brains’ immune systems have been activated on a long-term basis by repeated blast exposures and how the immune system may be affecting their brain function. Researchers hope this information could be helpful in treating TBI in service members and veterans who have been repeatedly exposed to blasts.

“This portion of the integrated project will provide data on the long-term consequences of persistent pathological inflammation in veterans with exposure to TBI,” said Elisabeth Wilde, a neuropsychologist at the Spencer Fox Eccles School of Medicine at University of Utah and a George E. Wahlen VA Health Research Scientist. “We hope to understand how immune responses influence brain structure and function so that we can identify and prevent continued secondary injury.”

The project’s final component will examine whether one of the brain’s main inflammatory responses, known as TNF-alpha, could be a useful target for treatments or preventive measures to protect against brain diseases in service members repeatedly exposed to low-level blasts. In a laboratory setting, researchers will use a drug that blocks the development of TNF-alpha to better understand how blocking this cause of inflammation could protect the brain.

“Our approach will shed light on whether a promising immune-related drug protects the brain following blast exposure. This work could translate into effective treatments for service members and law enforcement personnel who sustain TBI following blast,” said Dr. Rania Abutarboush, a neuroscientist at the Neurotrauma Department at the Naval Medical Research Center. “The findings may also help with the search for treatments for other brain diseases where the immune system is involved, such as Alzheimer’s disease.”