Objectives: To assess how biomarkers indicating central nervous system insult (neurobiomarkers) vary in peripheral blood with exertional-heat stress from prolonged endurance exercise. Design: Observational study of changes in neuron specific enolase (NSE), S100 calcium-binding protein B (S100β), Glial Fibrillary Acid Protein (GFAP) and Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) at Brighton Marathon 2022. Methods: In 38 marathoners with in-race core temperature (Tc) monitoring, exposure (High, Intermediate or Low) was classified by cumulative hyperthermia – calculated as area under curve of Time × Tc > 38 °C – and also by running duration (finishing time). Blood was sampled for neurobiomarkers, cortisol and fluid-regulatory stress surrogates, including copeptin and creatinine (at rested baseline; within 30 min of finishing; and at 24 h). Results: Finishing in 236 ± 40 min, runners showed stable GFAP and UCH-L1 across the marathon and next-day. Significant (P < 0.05) increases from baseline were shown post-marathon and at 24 h for S100β (8.52 [3.65, 22.95] vs 39.0 [26.48, 52.33] vs 80.3 [49.1, 99.7] ng·L −1) and post-marathon only for NSE (3.73 [3.30, 4.32] vs 4.85 [4.45, 5.80] μg·L −1, P < 0.0001). Whilst differential response to hyperthermia was observed for cortisol, copeptin and creatinine, neurobiomarker responses did not vary. Post-marathon, only NSE differed by exercise duration (High vs Low, 5.81 ± 1.77 vs. 4.69 ± 0.73 μg·L −1, adjusted P = 0.0358). Conclusions: Successful marathon performance did not associate with evidence for substantial neuronal insult. To account for variation in neurobiomarkers with prolonged endurance exercise, factors additional to hyperthermia, such as exercise duration and intensity, should be further investigated.
Bibliographical noteFunding Information:
The study was conducted at the Brighton Marathon held on 10th April 2022 in Brighton, United Kingdom (UK). Ethical approval was obtained from the UK Ministry of Defence Research and Ethics Committee (approval number 1030/MODREC/19) and complied with the standards set in the Declaration of Helsinki. The study was funded internally by the UK Surgeon General and practical support was given by Human Telemetrics (London, UK). The authors retained the right to collect, analyse and interpret data independently and to approve or disapprove publication of the finished manuscript.