Thomas Palin

Background and Objectives: Neurobiomarkers measured in peripheral blood can supplement management strategies following traumatic brain injury (TBI). Dual-assay of glial fibrillary acid protein (GFAP) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is FDA-approved to inform a decision threshold approach (GFAP >30 μg.L-1 and/or UCHL1 >360 μg.L-1) for post-TBI neuroimaging. As physical activity and thermal strain often accompany TBI-prone activities, we investigated whether each molecule’s quantification - and, by extension, clinical decisions - could be influenced by exercise-heat stress. Methods: In healthy volunteers monitored continuously for body core temperature (Tc), we used the i-STAT Alinity to assess plasma GFAP and UCHL1 responses to exercise in the laboratory (four female, eighteen male trained participants, cycling for 45 min in 32 °C) and field (three female and 22 male recreational marathon runners, finishing time 231± 34 min, peak ambient temperature 11 °C). Results: Respective ΔTc overall were 1.42 ± 0.37 °C and 1.87 [1.53, 2.31] °C. With laboratory exercise, GFAP and UCHL1 did not exceed the manufacturer’s decision threshold. Across the marathon, GFAP was stable, whereas UCH-L1 more than doubled (200 [200, 200] vs 462 [310, 782] μg.L-1, P<0.0001), breaching the decision threshold for neuroimaging in 18/25 runners. Discussion: Confounding from more severe exercise-heat stress should be considered when interpreting near-care assay of UCHL1 for TBI management.