Neuroimaging suggests that human consciousness relies on frequent access to default mode and dorsal attention brain networks.

Aims: We investigated whether human umbilical cord mesenchymal stem cell (hUC‐MSC)‐derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)‐induced neuroinflammation.Methods: Exosomes were isolated from hUC‐MSC supernatant by ultra‐high‐speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV‐2 cells, primary microglial cultures, and C57BL/6J mice. H₂O₂ was also used to induce inflammation and oxidative stress in BV‐2 cells. The effects of hUC‐MSC‐derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting.Results: Treatment with hUC‐MSC‐derived exosomes significantly decreased the LPS‐ or H₂O₂‐induced oxidative stress and expression of pro‐inflammatory cytokines (IL‐6 and TNF‐α) in vitro, while promoting an anti‐inflammatory (classical M2) phenotype in an LPS‐treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS‐induced NF‐κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF‐κB inhibitor BAY 11–7082 also inhibited the LPS‐induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti‐inflammatory and anti‐oxidative effects of the exosomes.Conclusion: hUC‐MSC‐derived exosomes ameliorated LPS/H₂O₂‐induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF‐κB/NLRP3 signaling pathway.

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also from systemic diseases, which seriously influence the quality of life and life expectancy of patients. As a highly selective anatomical and functional interface between the brain and systemic circulation, the blood-brain barrier (BBB) plays a pivotal role in maintaining brain homeostasis and normal function. The pathogenesis underlying cognitive decline may vary, nevertheless, accumulating evidences support the role of BBB disruption as the most prevalent contributing factor. This may mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress and excitotoxicity. However, direct evidence showing that BBB disruption causes cognitive decline is scarce, and interestingly, manipulation of the BBB opening alone may exert beneficial or detrimental neurological effects. A broad overview of the present literature shows a close relationship between BBB disruption and cognitive decline, the risk factors of BBB disruption, as well as the cellular and molecular mechanisms underlying BBB disruption. Additionally, we discussed the possible causes leading to cognitive decline by BBB disruption and potential therapeutic strategies to prevent BBB disruption or enhance BBB repair. This review aims to foster more investigations on early diagnosis, effective therapeutics, and rapid restoration against BBB disruption, which would yield better cognitive outcomes in patients with dysregulated BBB function, although their causative relationship has not yet been completely established.