NEURO-INFLAMMATORY RESPONSES TO EXTREME ENDURANCE EXERCISE IN ULTRA-MARATHON RUNNERS

High-endurance physical activity (HEPA) induces profound systemic stress, but its neurobiological correlates and recovery dynamics remain poorly characterized. We examined biomarkers of neuroaxonal stress and systemic inflammatory responses in ultra-marathon runners to characterize the acute and mid-term neurobiological effects of HEPA.
We prospectively studied 35 ultra-marathon runners (>42.195 km), collecting blood at baseline, immediately post-race, and at 1 week and 1.5 months. Serum NfL (neurofilament light chain), LDH (lactate dehydrogenase), pro-BNP (pro-brain natriuretic peptide), and CRP (C-reactive protein) were measured as markers of neuroaxonal stress, cellular damage, cardiac stress, and inflammation. Race characteristics were recorded to examine their moderating effects on biomarker trajectories.
The median age was 41 years (33.7–50.4), 82.9% were men, and the median race duration was 14 hours. After adjustment for age and sex, all biomarkers increased immediately post-race (NfL 1.15-fold, p=0.02; CRP 5.94-fold, p<0.001; LDH 1.32-fold, p<0.001; pro-BNP 1.52-fold, p<0.001). Race duration significantly moderated post-race biomarker trajectories (CRP, LDH, NfL), with longer races (>14 hours) associated with larger acute increases and delayed normalization (figure-A). Notably, better race performance
was associated with lower post-race NfL levels. Using age-adjusted reference thresholds, a substantial proportion of participants (44.1%) exhibited higher-than-expected baseline NfL levels (NfL+). Additionally, 71.4% of these individuals continued to exhibit higher-than-expected NfL levels at 1.5 months. Different patterns of response to and recovery from exercise were observed (figure-B).
HEPA elicits a transient neuro-inflammatory stress response with inter-individual variability in magnitude and recovery, suggesting distinct patterns of adaptive neuroaxonal dynamics.