Reactive oxygen species (ROS) and reactive nitrogen species can be produced by several cellular sources in the cardiovascular system. The nitroso/redox balance plays a major role in several pathophysiological processes. The inefficient removal of reactive species leads to detrimental effects on macromolecules inducing tissue dysfunction and ultimately cell death. Oxidative stress acts as a main contributor to cardiovascular diseases (CVD) (i.e., coronary heart disease, myocardial ischemia, hypertension, stroke, and heart failure) and cerebrovascular diseases (CeVD) (i.e. stroke, carotid stenosis, vertebral stenosis and intracranial stenosis, cerebral aneurysms, and vascular malformations). CVD are interconnected with the underlying atherosclerosis which damages medium and large arteries, while CeVD are linked to microcirculation alterations in blood flow resistance with profound implications for brain vascular pathophysiology. A complex interaction exists between the nervous and cardiovascular systems, and a dysfunction in one has a strong impact on the function of the other, leading to the disruption of a crucial neuro-cardiological network, where oxidative stress plays a crucial role. Selective cardiac pathologies compromise brain function and are associated with neurological disorders; similarly, different neurological conditions can induce a wide range of functional and structural alterations in the cardiovascular system.

The role of ROS in the onset and progression of vascular dysfunction is unquestionable. However, despite several pre-clinical and small clinical studies demonstrating that antioxidants are effective in inducing cardioprotection and neuroprotection, antioxidant therapies show disappointing results in large-scale randomized controlled trials. Therefore, understanding the actions of endogenous antioxidants (i.e., superoxide dismutase, catalase, glutathione peroxidase, thioredoxin reductase) and exogenous antioxidants is crucial in understanding the limitations of antioxidant therapies in CVD and CeVD. In particular, growing interest is given to endoplasmic reticulum-resident selenoproteins which display fundamental functions mostly related to oxidative cell balance control.

This Special Issue aims to cover the most recent findings on the role of oxidative and nitrosative stress in the brain-heart axis, highlighting how the cardiovascular and neurological systems mutually influence their pathophysiology. Pre-clinical (in vivo, ex vivo, in vitro, and in silico), translational and clinical studies, as well as critical review articles, are welcome. Through this invite, investigators will contribute to elucidating the role of oxidative and nitrosative stress in the pathophysiology and progression of CVD and CeVD and the impact of endogenous and exogenous antioxidant agents in a pathophysiological widespread context related to the heart/brain connection.

Potential topics include but are not limited to the following:

• Role of oxidative and/or nitrosative stress in different CVD, CeVD, and neurodegenerative diseases in the context of the heart/brain connection
• Role of endogenous and/or exogenous antioxidant agents in the pathophysiology of CVD, CeVD, and neurodegenerative diseases in the context of the heart/brain connection
• Strategies for prevention/treatment of oxidative and nitrosative stress-related vascular diseases in the heart, vessels, and brain
• Molecular mechanisms of oxidative and/or nitrosative stress in different diseases with related translational and clinical relevance
• Biomarkers of oxidative stress and/or nitrosative stress with diagnostic and/or prognostic value in CVD, CeVD, and neurodegenerative diseases in the context of the heart/brain connection