Effects of physical exertion on early changes in blood-based brain biomarkers: implications for the acute point of care diagnosis of concussion

Bazarian J, Abar B, Merchant-Borna K, Pham DL, Rozen E, Mannix R, Kawata K, Chou YY, Stephen SJ, Gill J. J Neurotrauma. 2022 Oct 6. doi: 10.1089/neu.2022.0267. Epub ahead of print. PMID: 36200628.


Take-Home Message

Physical exertion may alter some blood-based brain measures that investigators hope can help clinicians objectively diagnose a concussion.


An objective tool such as a blood-based biomarker (measures) could help diagnose acute concussions. However, many blood biomarkers related to brain inflammation can change due to physical exertion. Hence, we need more information regarding if and to what degree the change occurs during military and sporting events to make clinical decisions.

Study Goal

The authors assessed four blood-based biomarkers before and after a single workout of aerobic and resistance exercises to determine how these biomarkers changed after physical activity.


The authors recruited 30 collegiate football players (~19 years of age). Fifteen players underwent diffuse tensor imaging 24 hours before and 48 hours after a workout of strength and aerobic exercises. Blood was taken immediately before imaging and then again immediately after exertion and 45 later. The authors analyzed the blood for four biomarkers: 1) glial fibrillary acidic protein (GFAP), 2) ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and 3) neurofilament light  (NFL), and 4) tau. Players wore body sensors during the workout to measure distance (km), energy expenditure (kcal), player load (sum of all 3 planes of acceleration), and work ratio (% of time moving >1.5m/sec).On average, the workouts took 90 minutes.


Overall, two blood-based biomarkers changed after physical activity, and two did not. Specifically, GFAP decreased (median decrease 28%) immediately following the physical activity compared to baseline and returned to baseline within 45 minutes. In contrast, UCH-L1 was not immediately different from before exercise but increased within 45 minutes after exertion (median increased 37%). The changes in these first two biomarkers related to the duration of exercise. Specifically, someone would experience more biomarker changes if they exercised longer. The authors observed no differences over time for NFL, tau, or imaging outcomes.


The results suggest that just one bout of physical exertion initiates changes in some blood-based brain proteins without altered white matter integrity. This finding suggests that changes in two blood-based biomarkers levels are not due to changes within the white matter. The authors suggested that when commercial kits become available for clinicians to assess concussions, we may need to use an equation to account for exercise duration. This adjustment may not be needed if UCH-L1 is evaluated immediately after a concussion or if GFAP testing occurs after a sporting event (after the patient rested for 45 minutes). Furthermore, tau and NFL remained fairly stable over time; however, the authors acknowledged that these two biomarkers are less diagnostic during the first few hours after a concussion.

Clinical Implications

Medical professionals should continue to use multiple tests to make acute concussion diagnosis decisions. Additionally, they should be aware that more reliable, objective diagnostic tests may soon be commercially available, but we must consider optimizing their accuracy.

Questions for Discussion

Are biomarkers something you would be interested in using to assess concussions? If not, what are your concerns?

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Written by Jane McDevitt
Reviewed by Jeffrey Driban

Evidence-Based Assessment of Concussion Course - 5 EBP CEUs