Near-care assay of plasma glial fibrillary acid protein and ubiquitin carboxyl- terminal hydrolase isozyme L1: impact of exercise-heat stress

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 for assessing, at near-care, a decision threshold 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 investigate plasma GFAP and UCHL1 responses to exercise in the laboratory (three female, seven 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 also 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 prolonged exercise-heat stress should be considered when managing TBI using near-care assay of UCHL1.