Fig. 9.

Noise exposure induces neuronal activation with multiple targets for oxidative stress. First-line neuronal events in response to noise exposure are sleep disturbance (when exposed during the sleep phase) and stress response reactions linked with activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. This leads to the release of stress hormones (glucocorticoids and catecholamines) and secondary activation of the cerebral (and systemic) renin-angiotensin-aldosterone system (RAAS) as well as endothelin-1 expression. These potent triggers of inflammation and oxidative stress will lead to activation of NOX-2 via protein kinase C (PKC) and p47^phox phosphorylation, expression of inflammation markers and increased lipid peroxidation in the brain. Moreover, noise caused down-regulation of neuronal nitric oxide synthase (nNOS), and loss of antioxidant genes such as catalase (Cat) and forkhead box O3 (Foxo3) transcription factor. All these changes induce a neuroinflammatory phenotype with cerebral oxidative stress. These stress hormones and vasoconstrictors lead to similar adverse changes in the cardiovascular (and pulmonary) system, which may promote the development of manifest diseases, including cardiometabolic disease, dementia, and cancer. The HPA axis, sympathetic nervous system, RAAS, ET-1 expression, and neuroinflammation are redox-regulated and vice versa can induce oxidative stress via NOX-2 activation and other sources. CRH, corticotrophin-releasing hormone; ACTH, adrenocorticotrophic hormone; CVD, cardiovascular disease. Reused from Ref. [45] with permission.