Exercise training prevents the onset and the development of many chronic diseases, acting as an effective tool both for primary and for secondary prevention. Various mechanisms that may be the effectors of these beneficial effects have been proposed during the past decades: some of these are well recognized, others less. Muscular myokines, released during and after muscular contraction, have been proposed as key mediators of the systemic effects of the exercise. Nevertheless the availability of an impressive amount of evidence regarding the systemic effects of muscle-derived factors, few studies have examined key issues: (I) if skeletal muscle cells themselves are the main source of cytokine during exercise; (II) if the release of myokines into the systemic circulation reach an adequate concentration to provide significant effects in tissues far from skeletal muscle; (III) what may be the role carried out by muscular cytokine regarding the well-known benefits induced by regular exercise, first of all the anti-inflammatory effect of exercise. Furthermore, a greater part of our knowledge regarding myokines derives from the muscle of healthy subjects. This knowledge may not necessarily be transferred per se to subjects with chronic diseases implicating a direct or indirect muscular dysfunction and/or a chronic state of inflammation with persistent immune-inflammatory activation (and therefore increased circulating levels of some cytokines): cachexia, sarcopenia due to multiple factors, disability caused by neurological damage, chronic congestive heart failure (CHF) or coronary artery disease (CAD). A key point of future studies is to ascertain how is modified the muscular release of myokines in different categories of unhealthy subjects, both at baseline and after rehabilitation. The purpose of this review is to discuss the main findings on the role of myokines as putative mediators of the therapeutic benefits obtained through regular exercise in the context of secondary cardiovascular prevention.

Several studies link cardiovascular diseases (CVD) with unhealthy lifestyles (unhealthy dietary habits, alcohol consumption, smoking, and low levels of physical activity). Therefore, the strong need for CVD prevention may be pursued through an improved control of CVD risk factors (impaired lipid and glycemic profiles, high blood pressure, and obesity), which is achievable through an overall intervention aimed to favor a healthy lifestyle. Focusing on diet, different recommendations emphasize the need to increase or avoid consumption of entire classes of food, with only partly known and only partly foreseeable consequences on the overall level of health. In recent years, the ketogenic diet (KD) has been proposed to be an effective lifestyle intervention for metabolic syndrome, and although the beneficial effects on weight loss and glucose metabolism seems to be well established, the effects of a prolonged KD on the ability to perform different types of exercise and the influence of KD on blood pressure (BP) levels, both in normotensives and in hypertensives, are not so well understood. The objective of this review is to analyze, on the basis of current evidence, the relationship between KD, regular physical activity, and BP.

for many of the myokines identified to date, the information available is limited and not enough to characterize precise functions and activities carried out by those in man. Several issues need to be addressed by future studies, tailored to ascertain accurately and surely the biological role and the therapeutic potential of some myokines.

Exercise represents a unique case in which a single intervention is useful against a broad range of diseases and risk factors, this knowledge should lead to an ever-increasing use of this lifestyle change.

One of the major obstacles that prevents an effective therapeutic intervention against ischemic stroke is the lack of neuroprotective agents able to reduce neuronal damage; this results in frequent evolution towards a long-term disability with limited alternatives available to aid in recovery. Nevertheless, various treatment options have shown clinical efficacy. Neurotrophins such as brain-derived neurotrophic factor (BDNF), widely produced throughout the brain, but also in distant tissues such as the muscle, have demonstrated regenerative properties with the potential to restore damaged neural tissue. Neurotrophins play a significant role in both protection and recovery of function following neurological diseases such as ischemic stroke or traumatic brain injury. Unfortunately, the efficacy of exogenous administration of these neurotrophins is limited by rapid degradation with subsequent poor half-life and a lack of blood–brain-barrier permeability. Regular exercise seems to be a therapeutic approach able to induce the activation of several pathways related to the neurotrophins release. Exercise, furthermore, reduces the infarct volume in the ischemic brain and ameliorates motor function in animal models increasing astrocyte proliferation, inducing angiogenesis and reducing neuronal apoptosis and oxidative stress. One of the most critical issues is to identify the relationship between neurotrophins and myokines, newly discovered skeletal muscle-derived factors released during and after exercise able to exert several biological functions. Various myokines (e.g., Insulin-Like Growth Factor 1, Irisin) have recently shown their ability to protects against neuronal injury in cerebral ischemia models, suggesting that these substances may influence the degree of neuronal damage in part via inhibiting inflammatory signaling pathways. The aim of this narrative review is to examine the main experimental data available to date on the neuroprotective and anti-ischemic role of regular exercise, analyzing also the possible role played by neurotrophins and myokines.