An Oxidative Stress Biomarker for Noise-Associated Stroke: Evidence from Human and Mice.
BACKGROUND Occupational noise exposure is a recognized risk factor for stroke, yet biomarkers specific to noise-associated stroke (NAS) remain unclear. Oxidative stress (OS) plays a key mechanistic role in noise-induced cerebrovascular damage. We aim to identify OS biomarkers of NAS and conduct risk assessment. METHODS Candidate OS biomarkers were screened using Gene Expression Omnibus transcriptomic datasets integrated with eight machine-learning approaches, then verified in UK Biobank longitudinal data and in stroke model mice after 4-week noise exposure. In addition, the relationship between oxidative balance score (OBS) and stroke was evaluated among noise-exposed adults in the National Health and Nutrition Examination Survey (NHANES) 2005-2018 using logistic regression, and quartiles were applied to determine optimal cut-points. RESULTS Eight OS-related genes were identified, of which seven were validated in stroke mice. C-C Motif Chemokine Ligand 3 (CCL3) emerged as the key biomarker. In UK Biobank, occupational noise increased CCL3 expression (effect = 0.052, P = 0.038), and higher CCL3 levels predicted greater stroke risk (hazard ratio = 1.15, P < 0.001). Functionally, CCL3 drove neuroinflammation via chemokine signaling. In noise-exposed stroke mice, circulating CCL3 increased ( P = 0.014) and infarct volume enlarged by 12.9% ( P = 0.011). Among 3306 noise-exposed NHANES participants, higher OBS was protective (odd ratio [OR] = 0.97, P = 0.01), whereas OBS <10 markedly elevated stroke risk (OR = 2.40, P = 0.033) compared with the OBS >24 group. CONCLUSION CCL3 is a validated OS biomarker linking occupational noise exposure to stroke. Maintaining OBS >18 through dietary and lifestyle strategies may mitigate NAS risk and offer a targeted neuroprotective approach for noise-exposed populations.