Researchers Share Innovations for Protecting the Brain from Blast Effects

Photo By Paul Lagasse | Dr. Walter Carr, a brain health researcher at WRAIR, speaks at a panel discussion on...... read more read more

Photo By Paul Lagasse | Dr. Walter Carr, a brain health researcher at WRAIR, speaks at a panel discussion on the effects of blast exposure on brain health during the 8th International Forum on Blast Injury Countermeasures, May 3, 2024, at the MITRE Corporation in McLean, Virginia. Dr. Carr spoke about his efforts to develop standard thresholds for blast exposure that could be used in patient case evaluations and referrals.  see less | View Image Page

FORT DETRICK, MD, UNITED STATES

05.06.2024

Story by Paul Lagasse 

Medical Research and Development Command

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FORT DETRICK, Md. – Scientists from Walter Reed Army Institute of Research recently shared the results of their latest research into the effects of blast exposure on brain health with leading researchers from around the world at the 8th International Forum on Blast Injury Countermeasures in McLean, Virginia.

The annual conference, which took place May 1-3 in McLean, Virginia, was co-sponsored by the U.S. Army Medical Research and Development Command’s DOD Blast Injury Research Coordinating Office. As it has since its inception in 2015 as an information sharing agreement between the United States and Japan, the conference is a valuable opportunity to share the latest information and evidence-based approaches for preventing and treating injuries caused by the high-pressure shock waves emitted by explosions and heavy weapons fire.

Traumatic brain injuries caused by exposure to high pressure shock waves caused by explosions are a major concern in military medicine. According to the DOD, approximately 80% of injuries sustained by Warfighters in Operation Enduring Freedom and Operation Iraqi Freedom were caused by such shock waves, called blast overpressure. TBIs damage neurons in the brain, as well as the delicate fibers that connect nerves called axons and connective tissues in the nervous system called glia. A recent study by the U.S. Department of Veterans Affairs reported that almost 414,000 Service Members sustained a TBI between 2000 and late 2019. However, blast-induced injuries can be hard to diagnose because they don’t leave signs that can be detected during an exam, even when using advanced medical imaging. TBIs are often misdiagnosed as post-traumatic stress disorder, leading to delays in receiving proper treatment.

On the first day of the two-day panel session, Dr. Venkata Kakulavarapu, a senior research scientist in the Blast Induced Neurotrauma Branch at WRAIR’s Center for Military Psychiatry and Neurosciences, discussed his team’s research into developing a new tool for detecting changes in the permeability of the blood-brain barrier, which is one of the many potentially lethal secondary effects of blast overpressure. By injecting small clumps of fluorescent metal atoms – called nanoclusters – designed to mimic the shape of proteins into the bloodstream, they can follow the flow of blood through the brain and identify damaged blood vessels.

“Protein-templated fluorescent metal nanoclusters represent novel tools for measuring the blood-brain barrier disruption,” Kakulavarapu explained.

Dr. Mital Patel, a postdoctoral fellow with WRAIR’s Medical Readiness Systems Biology Branch, shared another novel approach to healing damage to the blood-brain barrier – through changes in diet, an approach he calls nutritional countermeasures. Patel’s research found that the typical Western diet – lacking two omega-3 polyunsaturated fatty acids called DHA and EPA and high in the omega-6 acids – appear to increase a person’s susceptibility to tissue injury induced by blast exposure. By changing Warfighters’ diets to include foods rich in omega-3 and by reducing the amounts of omega-6 to levels more proportional with omega-3, Patel says, their resistance to TBI and post-traumatic stress disorder could be significantly improved.

The neurochemical changes associated with cognitive disabilities in brains that have experienced TBI was the focus of a study conducted by Dr. James DeMar, a researcher with WRAIR’s Medical Readiness Systems Biology Branch in conjunction with WRAIR’s Blast-Induced Neurotrauma Branch. DeMar began by explaining that one of the challenges that doctors face when treating injured Warfighters is that the symptoms of TBI are often masked by the effects of other injuries, such as PTSD, which make accurate diagnosis difficult. DeMar’s study analyzed changes to proteins in the brain and the bloodstream within the first four hours after receiving a blast injury to see if there were any patterns unique to TBI that stood out from the effects of other forms of brain injury. DeMar found that blast exposure caused the levels of certain proteins to drop suddenly and then rebound. While the effect was noticeable in blood plasma proteins, it was significantly more pronounced in brain proteins.

DeMar said he and his team will be conducting more research to refine their understanding of the behaviors of blood and brain proteins following blast exposure and to assess the results to identify proteins that might be targetable by therapeutic drugs to better manage their regulation, thereby reducing the effects of the blast injury.

During the second day of the panel session, Dr. Aarti Gautam, also of the Medical Readiness Systems Biology Branch, shared the results of her team’s successful identification of telltale patterns in three types of microRNA – small segments of RNA that play an important role in gene expression – in the brains of test subjects that have been exposed to blast overpressure. These characteristic “fingerprints” in microRNA are not only useful for diagnosing blast-induced injury but may also help researchers develop therapeutic drugs that can treat the effects of blast injury.

“Whenever an individual faces a brain injury, there is a cascade of events that happens, very similar to a domino effect” Gautam explained. “When this domino effect happens, it happens immediately within milliseconds of the trauma exposure and followed by molecular events that happened immediately after that. So, it's very important to capture what happens within seconds post-trauma.”

Gautam’s research found that levels of microRNA in the blood are indeed correlated with injuries to brain tissue caused by blast overpressure. Future research will be conducted to more clearly establish patterns that doctors can look for in patients to diagnose TBI.

Not all challenges associated with TBI and other blast-induced brain injuries are medical or scientific in nature. In order to be eligible for VA health care, Service Members must be able to demonstrate that they received their injury while serving in the military. Typically, this is done by completing a military acute concussive evaluation, or MACE. However, MACE reviews are not routinely conducted for blast exposures encountered during training – a potentially dangerous oversight.

Dr. Walter Carr, a brain health researcher at WRAIR, was invited to speak about his efforts to address this shortcoming by developing standard thresholds for blast exposure, regardless of whether the exposure occurs in a training or an operational environment, which could be used in patient case evaluations and referrals. In partnership with the Oak Ridge Institute for Science and Education, Mercer University School of Medicine and the Naval Research Laboratory, Carr’s team conducted an extensive comparison of medical records of Service Members whose military occupational specialties indicated they were at risk of exposure to blast overpressure during their service. They then used the results of their analysis to develop a set of diagnostic criteria that doctors can use to assess the risk of mild TBI in patients over a long period of time.

The flowchart begins by determining the mechanism of injury (for example, the firing of a breaching charge), then examines clinical signs and symptoms, clinical examinations and imaging results gathered over time to determine the likelihood that a Service Member experienced a mild TBI at some point in their career.

“We are set up to look at acute exposure effects, but not so much chronic exposure effects, which is where I think the bigger concern is,” Carr said. “Across a period of months and more likely years, an individual may self-report headaches, tinnitus, brain fog, short-term memory loss and – more concerning – that it’s getting worse year after year. I think this is the real target.”

Carr and the other WRAIR scientists who participated in the IFBIC forum demonstrated that the organization is actively attacking the problem of blast overpressure induced TBI across a wide front, using the latest tools and techniques – and a lot of creative thinking – to develop new countermeasures against it that will save Warfighters’ lives not only on the battlefield, but long after they come home.