Biomarkers of Traumatic Brain Injury: The Brain Leaves Clues Long After the Injury

“My concussion was years ago…why do I still struggle?”

For decades, many veterans and first responders were told that a mild traumatic brain injury (mTBI) would heal within weeks or months. Yet thousands continue to experience brain fog, poor sleep, slowed thinking, headaches, irritability, memory problems, depression, and difficulty regulating emotions years later.

Today, researchers are discovering something important:

The brain often leaves measurable biological footprints long after the initial injury.

These “footprints,” known as biomarkers, are helping explain why symptoms persist even when a CT scan or MRI appears normal.

Study Spotlight

Blood Biomarkers Reveal Persistent Brain Changes Years After Military TBI

One of the largest military reviews published in the Journal of Neurotrauma summarized findings from the Chronic Effects of Neurotrauma Consortium (CENC) and other Department of Defense research programs evaluating veterans years after traumatic brain injury (Bazarian et al., 2025).

Researchers consistently identified elevations in several biomarkers that reflect different types of brain injury.

GFAP

GFAP is released when astrocytes, the brain’s support cells, become injured.

Persistent elevations suggest that changes involving astrocytes and the blood-brain barrier may continue long after the original injury.

Neurofilament Light Chain (NfL)

NfL is one of the best markers of axonal injury.

Multiple military studies found higher NfL concentrations in veterans years after deployment-related TBI, suggesting ongoing structural changes within nerve fibers.

Phosphorylated Tau

Tau proteins help stabilize neurons.

Elevated phosphorylated tau has been associated with poorer verbal memory and overlaps with proteins involved in Alzheimer’s disease and other neurodegenerative disorders.

What this means

Researchers are finding that concussion recovery is not always a single event. In some individuals, measurable biological changes remain long after symptoms were once expected to resolve.

Study Spotlight

TBI May Accelerate Biological Aging

A study published in the Journal of Head Trauma Rehabilitation examined post-9/11 veterans with deployment-related TBI using epigenetic aging clocks.

Researchers found evidence of accelerated biological aging compared with veterans who had not experienced TBI.

Rather than simply measuring age by birthdays, these biomarkers estimate how “old” cells behave biologically.

Although this field is still evolving, it suggests traumatic brain injury may influence long-term brain health beyond the initial injury.

Study Spotlight

MRI Shows the Brain’s Waste-Clearance System Changes After TBI

A study published in the Journal of Neurotrauma evaluated the brain’s glymphatic system using advanced MRI techniques.

Researchers found persistent alterations in glymphatic function among previously deployed veterans.

The glymphatic system helps clear metabolic waste, inflammatory proteins, and abnormal tau proteins, particularly during sleep.

When this system functions less efficiently, researchers believe it may contribute to persistent cognitive symptoms and increase vulnerability to neurodegenerative disease.

Study Spotlight

The Brain Can Look Normal but Function Differently

Researchers at the Marcus Institute for Brain Health used advanced eye-tracking technology to evaluate veterans years after concussion.

Despite appearing neurologically “normal” on routine examination, many participants demonstrated measurable deficits in:

• Attention

• Processing speed

• Eye movement coordination

• Cognitive efficiency

These findings reinforce an important point:

Not all brain injuries are visible on conventional imaging.

What Does This Feel Like?

These biological changes often look like everyday life becoming unexpectedly harder.

You may notice:

• Losing your train of thought

• Feeling mentally exhausted by simple tasks

• Irritability over small frustrations

• Poor sleep despite exhaustion

• Difficulty finding words

• Forgetting conversations

• Increased anxiety

• Feeling “different” than before the injury

Many veterans blame themselves.

The research increasingly suggests the brain itself may still be recovering.

What Can We Do?

No single treatment addresses every consequence of traumatic brain injury.

Recovery often requires addressing multiple systems simultaneously.

At Brain Treatment Center NoVA, our Veteran Reset Program combines evidence-informed approaches that may include:

• Precision neuromodulation

• Mental health therapy

• Occupational therapy through SPIN

• Functional medicine

• Hyperbaric oxygen therapy

• Nutritional optimization

• Sleep restoration

• Integrative psychiatry when appropriate

Because every brain injury is different, treatment should be individualized rather than one-size-fits-all.

The Bottom Line

One of the most important discoveries in military TBI research is this:

The brain remembers the injury long after the event itself.

Researchers continue to identify measurable biological changes involving neurons, glial cells, inflammation, aging, and brain waste clearance years after traumatic brain injury.

While biomarkers are still primarily research tools in many settings, they are fundamentally changing how we understand concussion recovery.

For veterans and first responders, that message is both validating and hopeful.

Persistent symptoms are increasingly understood as reflections of measurable brain biology, and understanding those changes is helping shape the future of individualized rehabilitation.

References

Bazarian, J. J., Zetterberg, H., Büki, A., Dengler, B. A., Diaz-Arrastia, R., Korley, F. K., Lazarus, R., Meier, T. B., Mondello, S., Okonkwo, D. O., Papa, L., Posti, J. P., Puccio, A. M.,

Steyerberg, E. W., Wang, K. K. W., Manley, G. T., & the NINDS TBI Classification and Nomenclature Initiative Blood-Based Biomarkers Working Group. (2025). Blood-based biomarkers for improved characterization of traumatic brain injury: Recommendations from the 2024 National Institute for Neurological Disorders and Stroke Traumatic Brain Injury Classification and Nomenclature Initiative Blood-Based Biomarkers Working Group. Journal of Neurotrauma, 42(13–14), 1065–1085. https://doi.org/10.1089/neu.2024.0581

Lippa, S. M., Gill, J., Brickell, T. A., French, L. M., & Lange, R. T. (2021). Blood biomarkers relate to cognitive performance years after traumatic brain injury in service members and veterans. Journal of the International Neuropsychological Society, 27(5), 508–514. https://doi.org/10.1017/S1355617720001071

Lippa, S. M., Gill, J., Brickell, T. A., French, L. M., & Lange, R. T. (2022). Blood biomarkers predict future cognitive decline after military-related traumatic brain injury. Current Alzheimer Research, 19(5), 351–363. https://doi.org/10.2174/1567205019666220331111154

Diaz-Arrastia, R., Wang, K. K. W., Papa, L., Sorani, M. D., Yue, J. K., Puccio, A. M., McMahon, P. J., Inoue, T., Yuh, E. L., Lingsma, H. F., Maas, A. I. R., Valadka, A. B., Okonkwo, D. O., & Manley, G. T. (2014). Acute biomarkers of traumatic brain injury: Relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. Journal of Neurotrauma, 31(1), 19–25. https://doi.org/10.1089/neu.2013.3040

Pignataro, G., et al. (2025). Blood-based biomarkers for traumatic brain injury. International Journal of Molecular Sciences, 26(24), 12158. https://doi.org/10.3390/ijms262412158

Brain Treatment Center NoVA provides comprehensive traumatic brain injury (TBI) care for active-duty military, veterans, first responders, and civilians throughout Northern Virginia and the Washington, DC region. Our multidisciplinary approach integrates mental health therapy, occupational therapy, functional medicine, precision neuromodulation, hyperbaric oxygen therapy, and brain health optimization to support individuals experiencing persistent symptoms following concussion or traumatic brain injury. We proudly serve patients using TRICARE, VA Community Care referrals when authorized, Aetna, and private pay options from Ashburn, Alexandria, Fairfax, Loudoun County, Arlington, Prince William County, and the greater Washington, DC metropolitan area