Research News and Highlights

Exciting Advancements in Blood-based Biomarkers of Sport-Related Concussion

According to research published in an AUG 2020 online issue of JAMA Network Open, higher concentrations of tau and lower concentrations of glial fibrillary acidic protein (GFAP) were associated with longer recovery times in male and female athletes who sustained a sport-related concussion.

The publication, entitled “Plasma Biomarker Concentrations Associated with Return to Sport Following Sport-Related Concussion in Collegiate Athletes- A Concussion Assessment, Research, and Education (CARE) Consortium Study” a product of a multi-center study that was supported by the Department of Defense (DoD), the National Collegiate Athletic Association (NCAA), and the National Institutes of Health (NIH). 

This study assessed preseason and post-injury results from clinical tests and blood collections in 127 collegiate athletes (e.g., 97 male, 30 female) who sustained a sport-related concussion while competing in a contact sport (e.g., football, ice hockey, soccer, rugby, and lacrosse) at the six Advanced Research Core (ARC) sites of the NCAA-DoD CARE Consortium. What makes this study unique is the inclusion of student athletes from the U.S. Military Academy at West Point and the U.S. Air Force Academy.  

Dr. Jessica Gill and Dr. Cassandra Pattinson, of the National Institute of Nursing Research, assessed the pre and post-injury blood samples and found that the 62 (e.g., 46 male, 16 female) athletes who took 14 days or longer to return to play after injury had higher total tau concentrations (p=0.02) and lower GFAP concentrations (p=0.04). The two return to play groups (e.g., the 65 athletes who returned to sport >14 days after injury and the 62 athletes who returned to sport ≤ 14 days after injury) didn’t differ demographically (e.g., age, gender, or number of prior concussions) and had similar tau and GFAP concentrations in the preseason blood collection (e.g., before their sport-related concussion). 

These results are consistent with previous studies, which found that higher concentrations of total tau is related to longer return to sport time after sport-related concussion in collegiate and professional athletes. [1],[2],[3]. These preliminary findings emphasize the potential blood-based biomarkers, such as tau and GFAP, have in tracking neuronal recovery after a traumatic brain injury. Efforts are already underway for continued assessment of these athletes, following them through their collegiate careers to better determine the cumulative and persistent effects of sport-related concussion.

[1] Gill, J., Merchant-Borna, K., Jeromin, A., Livingston, W., & Bazarian, J. (2017). Acute plasma tau relates to prolonged return to play after concussion. Neurology, 88(6), 595–602. https://doi.org/10.1212/WNL.0000000000003587

[2] Shahim, P., Tegner, Y., Wilson, D. H., Randall, J., Skillbäck, T., Pazooki, D., Kallberg, B., Blennow, K., & Zetterberg, H. (2014). Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA neurology, 71(6), 684–692. https://doi.org/10.1001/jamaneurol.2014.367

[3] Shahim, P., Tegner, Y., Marklund, N., Blennow, K., & Zetterberg, H. (2018). Neurofilament light and tau as blood biomarkers for sports-related concussion. Neurology, 90(20), e1780–e1788. https://doi.org/10.1212/WNL.0000000000005518

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CNRM Investigator named winner of the Military Health System's 2020 "Outstanding Research Accomplishment" Award 

Jessica Gill, PhD, RN, FAAN, was one of the four individuals and two teams throughout the entire Military Health System to be recognized for their outstanding skills and contributions that support the health and readiness of the U.S. Armed Forces. Dr. Gill is CNRM's NIH Deputy Director and Co-PI of CNRM's Biomarkers Core. She is also the Acting Deputy Director of the National Institute of Nursing Research (NINR). She was nominated by her peers and selected for her high impact and invaluable contributions to diagnostic and prognostic traumatic brain injury (TBI) blood-based biomarker research. Her award is listed on the Military Health System's annual Research Symposium's website and was also featured in a 23JUL2020 Military Health System article.

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CNRM's Pioneering Efforts in Investigating Blood-based Biomarkers of Traumatic Brain Injury 

Currently, no blood-based biomarker can objectively diagnose traumatic brain injury (TBI); however, results from two recently published CNRM collaborative studies emphasize the strong potential of neurofilament light (NfL)— a protein found in the skeleton of axons that gives sensitive indication of neuronal damage. 

The first study assessed NfL, tau, glial fibrillay acidic protein (GFAP), and ubiquitin c-terminal hydrolase-L1 (UCH-L1) in serum samples that were collected from 230 civilian participants (e.g., 162 persons with varying TBI severities and 68 controls) at various time points, ranging from 30 days to 5 years post-injury. The results found that:

  • At 30 days, NfL concentrations were 2.0 times higher in TBI patients (of all severities) than controls (p<0.0001)
  • With high accuracy, NfL concentrations distinguished TBI patients (of all severities) from controls at 30, 90, and 180 days
  • At 30 days, NfL concentrations in TBI patients corresponded with injury severity (e.g., mild, moderate, or severe) and functional outcomes (e.g., scores on the Glasgow Outcome Scale)
  • The relationship between the other serum biomarkers and severity of TBI and functional outcomes were weak

These results closely correlate with the second study, which examined NfL concentrations in professional Swedish ice hockey players. The cohort was comprised of 118 participants: 45 players with acute concussion; 31 players with repetitive concussion and post-concussive symptoms; 28 preseason controls; and 14 non-athletic controls. The results found that:

  • Of the 45 players with acute concussion, NfL concentrations were 1.3 times higher in players who returned to play after more than 10 days post-injury, compared to those who returned to play in less than 10 days (p=0.020)
  • Of the 31 players with repetitive concussion and post-concussive symptoms, NfL concentrations were 2.0 times higher in players who experienced symptoms more than a year post-injury, compared to players whose symptoms resolved in less than a year (p=0.0011)

Although additional research is needed before any conclusive statements can be made, CNRM's efforts mark NfL as an increasingly viable contender in the quest for blood-based biomarkers of TBI. 

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