Researchers, backed by an $8 million grant from the United States Department of Defense, will investigate how to better prevent traumatic brain injury, or TBI, in military personnel exposed to shock waves.
The research team from the US Naval Medical Research Center, UVA Health, Johns Hopkins University and the University of Utah will examine the role of brain inflammation in traumatic brain injury following explosion exposure, to understand the role of brain inflammation in TBI, as well as how previous exposure to an explosion affects the brain inflammation. The goal: to identify potential treatment options and ways to block brain inflammation and TBI.
This effort is the culmination of several years of intensive research by members of this collaborative team to understand the risks of repeated detonations during a military career. This new grant will expand recent work related to neuroinflammation in the brain that may underlie physiological changes resulting from exposure to explosions. Our efforts could pave the way for new pharmacological treatments for blast exposure and could have implications for other conditions such as long-term COVID where brain inflammation can occur.”
Capt. Stephen Ahlers (retired), PhD, Program Leader, US Naval Medical Research Center
Understanding Brain Inflammation
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 draws from active and retired military personnel who are repeatedly exposed to explosions during training and operations, researchers in one part of the project will try to better understand how the immune system may contribute 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 workers from the effects of repeated exposure to low-level blasts,” said James Stone, MD, PhD, a University of Virginia School of Medicine radiologist. Using advanced brain imaging to directly visualize inflammation, along with blood sampling, we hope to gain a better understanding of how the brain and immune system respond to explosion exposure.”
Causes of Long-Term TBI Symptoms
While most service workers recover from TBI within weeks, about a third will have long-lasting symptoms. The second component of the project aims to identify inflammatory markers in the brain associated with longer recovery times from a TBI, which may help identify service workers at higher risk of poor outcomes following a brain injury and identify possible treatment options.
“Our new laboratory methods regarding brain-derived exosomes provide a unique opportunity to understand pathological changes that may be related to the chronic symptoms seen in military personnel and veterans. Combining this with the new imaging methods will further enhance our understanding of exposure to explosions dramatically.” said Jessica Gill, PhD, RN, a researcher with the Johns Hopkins School of Nursing.
Veterans with chronic TB
In the third component of the project, researchers will use brain imaging and blood sampling from veterans diagnosed with chronic TBI to determine whether their brain’s immune systems are activated long-term by repeated exposure to blasts and how the immune system may affect their brains. . function. Researchers hope this information may be helpful in treating TBI in service personnel and veterans who have been repeatedly exposed to blasts.
“This part of the integrated project will provide data on the long-term consequences of persistent pathological inflammation in veterans with exposure to TBI,” said Dr. Elisabeth Wilde, PhD, a neuropsychologist at the Spencer Fox Eccles School of Medicine at the University of Utah. and a George E. Wahlen VA Health Research Scientist. “We hope to understand how immune responses affect brain structure and function so that we can identify and prevent continued secondary injury.”
A potential treatment target for brain diseases
The final strand of the project will examine whether one of the brain’s key inflammatory responses, known as TNF-alpha, could be a useful target for treatments or preventative measures to protect against brain disease in military personnel repeatedly exposed to low-level blasts. . In a lab setting, researchers will use a drug that blocks the development of TNF-alpha to better understand how blocking this cause of inflammation might protect the brain.
“Our approach will shed light on whether a promising immune-related drug protects the brain after blast exposure. This work could translate into effective treatments for service workers and law enforcement officers who support TBI after a blast,” said Dr. Rania Abutarboush, PhD, a neuroscientist in the Neurotrauma Division of the Naval Medical Research Center. “The findings may also help search for treatments for other brain diseases involving the immune system, such as Alzheimer’s disease.”
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