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1.
Proc Natl Acad Sci U S A ; 118(44)2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34702739

RESUMEN

Inflammation drives the pathology of many neurological diseases. d-mannose has been found to exert an antiinflammatory effect in peripheral diseases, but its effects on neuroinflammation and inflammatory cells in the central nervous system have not been studied. We aimed to determine the effects of d-mannose on key macrophage/microglial functions-oxidative stress and phagocytosis. In murine experimental autoimmune encephalomyelitis (EAE), we found d-mannose improved EAE symptoms compared to phosphate-buffered saline (PBS)-control mice, while other monosaccharides did not. Multiagent molecular MRI performed to assess oxidative stress (targeting myeloperoxidase [MPO] using MPO-bis-5-hydroxytryptamide diethylenetriaminepentaacetate gadolinium [Gd]) and phagocytosis (using cross-linked iron oxide [CLIO] nanoparticles) in vivo revealed that d-mannose-treated mice had smaller total MPO-Gd+ areas than those of PBS-control mice, consistent with decreased MPO-mediated oxidative stress. Interestingly, d-mannose-treated mice exhibited markedly smaller CLIO+ areas and much less T2 shortening effect in the CLIO+ lesions compared to PBS-control mice, revealing that d-mannose partially blocked phagocytosis. In vitro experiments with different monosaccharides further confirmed that only d-mannose treatment blocked macrophage phagocytosis in a dose-dependent manner. As phagocytosis of myelin debris has been known to increase inflammation, decreasing phagocytosis could result in decreased activation of proinflammatory macrophages. Indeed, compared to PBS-control EAE mice, d-mannose-treated EAE mice exhibited significantly fewer infiltrating macrophages/activated microglia, among which proinflammatory macrophages/microglia were greatly reduced while antiinflammatory macrophages/microglia increased. By uncovering that d-mannose diminishes the proinflammatory response and boosts the antiinflammatory response, our findings suggest that d-mannose, an over-the-counter supplement with a high safety profile, may be a low-cost treatment option for neuroinflammatory diseases such as multiple sclerosis.


Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Manosa/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Animales , Evaluación Preclínica de Medicamentos , Femenino , Manosa/farmacología , Ratones Endogámicos C57BL , Imagen Molecular
2.
Magn Reson Imaging Clin N Am ; 32(2): 375-384, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38555147

RESUMEN

Neuroinflammation is a key immune response observed in many neurologic diseases. Although an appropriate immune response can be beneficial, aberrant activation of this response recruits excessive proinflammatory cells to cause damage. Because the central nervous system is separated from the periphery by the blood-brain barrier (BBB) that creates an immune-privileged site, it has its own unique immune cells and immune response. Moreover, neuroinflammation can compromise the BBB causing an influx of peripheral immune cells and factors. Recent advances have brought a deeper understanding of neuroinflammation that can be leveraged to develop more potent therapies and improve patient selection.


Asunto(s)
Inflamación , Enfermedades Neuroinflamatorias , Humanos , Inflamación/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Sistema Nervioso Central
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