Stroke is currently the second most common cause of death worldwide and a major cause of serious long-term morbidity. Selenium is a trace element with pleotropic effects on human health. Selenium deficiency has been associated with a prothrombotic state and poor immune response, particularly during infection. Our aim was to synthesize current evidence on the tripartite interrelationship between selenium levels, stroke, and infection. Although evidence is contradictory, most studies support the association between lower serum selenium levels and stroke risk and outcomes. Conversely, limited evidence on the role of selenium supplementation in stroke indicates a potentially beneficial effect of selenium. Notably, the relationship between stroke risk and selenium levels is bimodal rather than linear, with higher levels of serum selenium linked to disturbances of glucose metabolism and high blood pressure, morbidities which are, in turn, substrates for stroke. Another such substrate is an infection, albeit forming a bidirectional relationship with both stroke and the consequences of impaired selenium metabolism. Perturbed selenium homeostasis leads to impaired immune fitness and antioxidant capacity, which both favor infection and inflammation; specific pathogens may also contend with the host for transcriptional control of the selenoproteome, adding a feed-forward loop to this described process. Broader consequences of infection such as endothelial dysfunction, hypercoagulation, and emergent cardiac dysfunction both provide stroke substrates and further feed-forward feedback to the consequences of deficient selenium metabolism. In this review, we provide a synthesis and interpretation of these outlined complex interrelationships that link selenium, stroke, and infection and attempt to decipher their potential impact on human health and disease. Selenium and the unique properties of its proteome could provide both biomarkers and treatment options in patients with stroke, infection, or both.

Epidemiological, clinical, and radiological studies have provided insights into the phenomenology and biological basis of cognitive impairment in COVID-19 survivors. Furthermore, its association with biomarkers associated with neuroinflammation and neurodegeneration supports the notion that it is a distinct aspect of LongCOVID syndrome with specific underlying biology. Accounting for the latter, translational studies on SARS-CoV-2's interactions with its hosts have provided evidence on type I interferon dysregulation, which is seen in neuroinflammatory and neurodegenerative diseases. To date, studies attempting to describe this overlap have only described common mechanisms. In this manuscript, we attempt to propose a mechanistic model based on the host-virus interaction hypothesis. We discuss the molecular basis for a SARS-CoV-2-associated neurocognitive disorder (SAND) focusing on specific genes and pathways with potential mechanistic implications, several of which have been predicted by Vavougios and their research group. Furthermore, our hypothesis links translational evidence on interferon-responsive gene perturbations introduced by SARS-CoV-2 and known dysregulated pathways in dementia. Discussion emphasizes the crosstalk between central and peripheral immunity via danger-associated molecular patterns in inducing SAND's emergence in the absence of neuroinfection. Finally, we outline approaches to identifying targets that are both testable and druggable, and could serve in the design of future clinical and translational studies.

Repulsive guidance molecule-a (RGMa) has emerged as a significant therapeutic target in a variety of neurological disorders, including neurodegenerative diseases and acute conditions. This review comprehensively examines the multifaceted role of RGMa in central nervous system (CNS) pathologies such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, neuromyelitis optica spectrum disorder, spinal cord injury, stroke, vascular dementia, auditory neuropathy, and epilepsy. The mechanisms through which RGMa contributes to neuroinflammation, neuronal degeneration, and impaired axonal regeneration are herein discussed. Evidence from preclinical studies associate RGMa overexpression with negative outcomes, such as increased neuroinflammation and synaptic loss, while RGMa inhibition, particularly the use of agents like elezanumab, has shown promise in enhancing neuronal survival and functional recovery. RGMa’s responses concerning immunomodulation and neurogenesis highlight its potential as a therapeutic avenue. We emphasize RGMa’s critical role in CNS pathology and its potential to pave the way for innovative treatment strategies in neurological disorders. While preclinical findings are encouraging so far, further clinical trials are needed to validate the safety and efficacy of RGMa-targeted therapies.

The aim of this study was to evaluate the effect of a 4-week respiratory muscle training (RMT) intervention versus continuous positive airway pressure (CPAP) on cardiorespiratory parameters and cognitive function in patients with OSA. Twenty-eight male patients with OSA were divided into two groups (RMT_group n = 14 and CPAP_group n = 14) and we recorded cardiopulmonary parameters and completed the questionnaires for cognitive impairment (MoCA) and sleep quality (PSQI) before and after 4 weeks. We observed differences before and after the intervention in cardiopulmonary parameters: RMT_group: breathing reserve (p < 0.001) and oxygen breathing (p = 0.002), at the end of the exercise test and pulse-respiratory quotient at rest (p < 0.001), end of exercise (p = 0.020), and recovery (p < 0.001), mean arterial pressure (RMT_groupp = 0.035, CPAP_groupp = 0.032); cognitive function assessment: RMT_group: 7% improvement in MoCA_score (p < 0. 001). and in the attention–working memory domain by 13% (p = 0.001), CPAP_group: improvement in the short-term memory recall domain by 28% (p = 0.001) and in the visuospatial domain by 18% (p = 0.027); sleep quality scores: RMT_group: 22% improvement in PSQI_score (p = 0.013), and 50% reduction in ‘cannot breathe comfortably’ domain (p = 0.013), CPAP_group: 31% increase in ‘waking in the middle of the night or early in the morning’ domain (p = 0.044). Our findings support the implementation of RMT programs in patients with OSA as an effective and beneficial practice to promote exercise and reduce symptoms of sleep disturbance.