Biomarkers: Unlocking the Hidden Threat of Brain Injury From Blast Overpressure

TYSONS CORNER, Va. — Traumatic brain injury resulting from blast exposure has been described as the signature threat of the modern battlefield, impacting over 490,000 U.S. Servicemembers since 2000. While the vast majority of these TBIs (around 80-85%) are classified as mild TBI (mTBI), the true incidence is likely far greater. Brain injury caused by sub-concussive events, such as repeated exposure to low-level blast waves during heavy-weapons training, can inflict damage at a subcellular level. These blast overpressure injuries can cause progressive cognitive and peripheral organ damage, and their effects may be cumulative. Repeated exposure to sub-concussive blasts can cause not only acute, but potentially long-term pathophysiological effects and neurobehavioral changes that can significantly impact Servicemember health and readiness.

The symptoms of BOP are varied, vague, and frequently delayed, often mimicking other conditions like PTSD. This complex and elusive presentation makes accurate diagnosis challenging. Current assessment tools are often insufficient, raising concerns about both under-diagnosis and over-triage, and allowing the problem to remain a hidden enemy.

To combat this, Drs. Hammamieh and Gautam in collaboration with Blast-Induced Neurotrauma Branch researchers at the Walter Reed Army Institute of Research, a direct reporting unit of the Defense Health Agency Research & Development-Medical Research & Development Command, are pioneering a new approach: biomarkers. "Our research has identified changes in proteins that occur very soon after blast exposure. These changes are linked to biological processes involved in blood vessel injury, clotting, inflammation, and damage to brain cells and their support structures. By mapping these early molecular changes, we hope to identify biomarkers that could one day enable rapid field tests to detect blast-related injury sooner," said Dr. Hammamieh. This research could give commanders and clinicians earlier, more objective insight into whether a Servicemember has been affected by blast exposure long before symptoms appear, helping inform triage, recovery, and return-to-duty decisions.

This expertise in biomarker identification is not new to DHA R&D-MRDC; its research has been instrumental in identifying blood biomarkers for other critical military health conditions, such as heat and cold stress, acute mountain sickness, exposure to environmental stressors and traumatic events, and the risk of sepsis, demonstrating a broad capability in molecular diagnostics, prognostics, and the development of novel therapeutic interventions. Researchers have identified key molecular changes that occur both in the acute and chronic stages of blast exposure. Mapping these blast-induced molecular changes may help identify preemptive diagnostic biomarkers to support triage and removal from exposure. They can also help identify potential therapeutic targets.

While Food and Drug Administration-cleared tests and devices using biomarkers to diagnose more severe TBI are already in use, they typically require samples to be sent to a lab for analysis. The challenge for blast overpressure is to develop rapid, point-of-care solutions that can inform fast decision-making in dynamic, far-forward environments.

The Complexity of the Invisible Enemy

Blast overpressure is also more complex than acute blast exposure. Assessing the effect of repeated exposure to low-level blasts is a "multi-parameter problem," as highlighted by experts at the recent 10th International Forum on Blast injury Countermeasures. While research has already helped establish initial thresholds for blast exposure and recommended risk-management actions, the precise dose-response relationship remains a critical unknown. The severity of blast impact is affected by a multitude of variables, including: the specific weapons system, Servicemember's position, environmental conditions, number of exposures, and protective equipment.

Because the vast majority of this type of injury comes from exposure generated when Servicemembers fire their own weapons – whether during training or in contested environments – prevention is key. Commanders need to know more about the dose–response relationship in order to preserve readiness and protect Servicemember health both in the near and long term.

This urgent need has galvanized researchers from multiple countries and disciplines, each working to identify the best biomarker to reveal this hidden threat and give commanders the evidence-based information they need to make critical decisions.

IFBIC: A Force Multiplier in Biomarker Research

The IFBIC forum serves as a vital platform for advancing this complex research. Through events like IFBIC, DHA R&D, MRDC is strengthening international partnerships to share data, best practices, and countermeasures. This collaborative approach, working with allies and transcending traditional boundaries, is a force multiplier in accelerating blast injury research. Current research, fostered by these collaborations, will significantly improve the detection, prevention, and treatment of blast-related brain injuries.