An Oxidative Stress Biomarker for Noise-Associated Stroke: Evidence from Human and Mice

Abstract

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.