Obstructive sleep apnea (OSA) is highly prevalent but easily undiagnosed and is an independent risk factor for cognitive impairment. However, it remains unclear how OSA is linked to cognitive impairment. In the present study, we found the correlation between morphological changes of perivascular spaces (PVSs) and cognitive impairment in OSA patients. Moreover, we developed a novel set of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate the fluid dynamics of glymphatic drainage system. We found that the inflow and outflow parameters of the glymphatic drainage system in patients with OSA were obviously changed, indicating impairment of glymphatic drainage due to excessive perfusion accompanied with deficient drainage in OSA patients. Moreover, parameters of the outflow were associated with the degree of cognitive impairment, as well as the hypoxia level. In addition, continuous positive airway pressure (CPAP) enhances performance of the glymphatic drainage system after 1 month treatment in OSA patients. We proposed that ventilation improvement might be a new strategy to ameliorate the impaired drainage of glymphatic drainage system due to OSA-induced chronic intermittent hypoxia, and consequently improved the cognitive decline.

Studies implicate that gut dysbiosis is related with many neurological diseases. However, the potential role of gut dysbiosis in cryptogenic stroke (CS) has not been elucidated yet. In this study, a high prevalence of gastrointestinal (GI) dysfunction and gut inflammation with increased intestinal permeability have been found in CS patients compared with normal controls (NCs). The systemic inflammation in CS patients was also identified by measuring the levels of plasma C-reactive protein (CRP), lipopolysaccharide (LPS), LPS-binding protein (LBP), and white blood cells (WBC) count. Using 16S rRNA sequencing, we found increased alpha diversity, accompanied by a higher abundance of Enterobacteriaceae, Streptococcaceae, and Lactobacillaceae at the family level and Escherichia–Shigella, Streptococcus, Lactobacillus, and Klebsilla at the genus level in the intestinal microbiota of CS patients compared to NCs. Our results showed that the abundance of Klebsilla was positively correlated with the systemic inflammation, the National Institutes of Health Stroke Scale (NIHSS) scores, and the infarct volumes. In conclusion, gut dysbiosis in CS patients was associated with the severity of CS and the systemic inflammation. Maintaining the intestinal homeostasis may be a potential strategy for the treatment of CS.

IntroductionGeneralized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood.Materials and methodsWe characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation.ResultsOur findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response.ConclusionsThese findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.