# 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.

## Key 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.