Near-care assay of plasma glial fibrillary acid protein and ubiquitin carboxyl-terminal hydrolase isozyme L1 with shorter and prolonged duration exercise

TL;DR

This study examines how exercise and heat stress affect blood levels of two brain injury biomarkers, GFAP and UCHL1, to determine if they might interfere with TBI diagnosis.

Contribution

The study reveals that UCHL1 levels can rise significantly during prolonged exercise, potentially leading to false positives in TBI diagnosis.

Findings

UCHL1 levels more than doubled during a marathon, exceeding the decision threshold for neuroimaging in 18 out of 25 runners.

GFAP levels remained stable during both laboratory and field exercise conditions.

Exercise-heat stress may confound UCHL1 interpretation in traumatic brain injury management.

Abstract

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. 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). 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. Confounding from more severe exercise-heat stress should be considered when interpreting near-care assay of UCHL1 for TBI management.

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