Thermoregulatory and plasma neurobiomarker responses to heat tolerance assessment in exertional heat illness and matched controls

Exercise in the heat and elevated tissue temperature are associated with neuronal stress and changes in blood-brain barrier (BBB) function. More severe thermal insult may manifest as exertional heat illness (EHI) and complication by central nervous system (CNS) dysfunction may persist post-EHI. We investigated neurobiomarkers associated with neuronal injury (brain-derived tau, BD-tau; neurofilament light, NfL; ubiquitin carboxyl-terminal hydrolase isozyme L1, UCH-L1) and BBB function (glial fibrillary acid protein, GFAP) in the peripheral blood of 34 recent (∼4 months) EHI patients and 30 Control individuals without prior EHI history, matched for variables influencing thermoregulation. Participants completed an exercise heat tolerance assessment (HTA), with neurobiomarkers measured pre- and post-HTA. An equal number of participants (n=6) in both EHI and Control groups showed thermoregulatory responses consistent with thermal intolerance. Pooled changes in BD-tau, GFAP and UCH-L1 showed moderate to large effect sizes (Cohen’s d =1.2, -1.3 and 0.75), including novel elevation in BD-tau (4.84 [4.10, 5.51] vs. 6.89 [5.69, 7.85] pg.mL^-1), whereas impact of HTA on NfL was negligible (Cohen’s d=0.03). No differences were evident in neurobiomarker response between EHI and Controls (time x group interaction P=0.244), and no consistent associations between body core temperature and neurobiomarker concentrations were demonstrated. In conclusion, neurobiomarker responses to HTA were similar between EHI cases and Controls, indicating an absence of ongoing CNS injury in this patient cohort. However, variability in neurobiomarkers with HTA queries the general applicability of these biochemical surrogates in the management of brain insult associated with prior exercise and thermal stress.