Sepsis and the orexin system

Hirota, Kazuyoshi

doi:10.1007/s00540-016-2246-6

Cited by 6 publications

(5 citation statements)

References 32 publications

(42 reference statements)

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“…The apical administration of OX-A was able to prevent the production of ROS induced by LPS in basolateral cortical microglia cells, in a manner also mediated by OX-1R. In agreement with our findings, recent studies have revealed that the peripheral administration of OX-A results in increased survival of mice with LPS-mediated septic shock by inhibiting the excessive production of inflammatory cytokines (28).…”

Section: Discussionsupporting

confidence: 91%

Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier

et al. 2019

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In states of intestinal dysbiosis, a perturbation of the normal microbiome composition, the intestinal epithelial barrier (IEB) permeability is increased as a result of the disruption of the epithelial tight junction protein network, in which occludin is mostly affected. The loss of IEB integrity promotes endotoxemia, that is, bacterial lipopolysaccharide (LPS) translocation from the intestinal lumen to the circulatory system. This condition induces an enhancement of pro-inflammatory cytokines, which leads to neuroinflammation through the gut-brain axis. Orexin-A (OX-A), a neuropeptide implicated in many physiological functions and produced mainly in the brain lateral hypothalamic area, is expressed also in several peripheral tissues. Orexin-producing neurons have been found in the myenteric plexus to project to orexin receptor 1 (OX-1R)-expressing enterocytes of the intestinal villi. In the present study we investigated the protective role of OX-A against LPS-induced increase of IEB permeability and microglia activation in both an in vivo and in vitro model of the gut-brain axis. By exploiting biochemical, immunocytochemical, immunohistochemical, and functional approaches, we demonstrate that OX-A preserves the IEB and occludin expression, thus preventing endotoxemia and subsequent neuroinflammation.

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Section: Discussionsupporting

confidence: 91%

Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier

et al. 2019

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“…The OXergic neurons could degenerate by neuroinflammation with the decline of OXergic activity, which may partly characterize the symptoms of sepsis [ 12 ]. Indeed, we recently found that LPS significantly reduced OXA contents in the pons containing the locus coeruleus which may impair sympathetic nervous system [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma orexin A does not reflect severity of illness in the intensive care units patients with systemic inflammation

et al. 2022

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Background Systemic inflammatory response occurs by sepsis and invasive surgery. Recent articles suggest that not only CRP but also procalcitonin, presepsin, and neutrophil gelatinase-associated lipocalin may reflect the severity of systemic inflammation. In addition, as systemic inflammation could degenerate orexin neurons, plasma orexin A might also be a good biomarker to predict the severity. Thus, we have determined relation between plasma biomarker and severity of illness score in patients with systemic inflammation. Methods Previous database (UMIN000018427) was used to secondly determine which plasma biomarkers may predict the severity of illness in the ICU patients with systemic inflammation (n = 57, 31 non-sepsis surgical patients and 26 sepsis patients). We measured plasma levels of orexin A, CRP, procalcitonin, presepsin, and neutrophil gelatinase-associated lipocalin were measured, and APACHE II score was assessed in these patients at their admission to the ICU. Data are shown as mean ± SD. Statistical analyses were done with unpaired t test. The correlation between APACHE II score and plasma biomarkers were examined using Pearson’s correlation coefficient and a least squares linear regression line. Results Demographic data did not differ between sepsis and non-sepsis groups. However, APACHE-II score was significantly higher in sepsis group than those in non-sepsis group (20.9 ± 6.6 vs 15.8 ± 3.2, p < 0.01). There were significant correlations between APACHE II score and plasma CRP (r = 0.532, p < 0.01), procalcitonin (r = 0.551, p < 0.01), presepsin (r = 0.510, p < 0.01), and neutrophil gelatinase-associated lipocalin (r = 0.466, P < 0.01) except orexin A. Conclusion All plasma biomarkers tested except orexin A may reflect the severity of illness in patients with systemic inflammation.

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“…Conversely, the intravenous injection of OXA reverted these clinical signs. Other reports indicate that LPS or TNFα (a major cytokine involved in septic shock) were also able to suppress orexin neuronal activity (159). More recently, the use of orexin-neuron ablated mouse model (OX/ataxin-3 transgenic mouse model) injected with LPS revealed a high mortality rate as compared to wild type mice (160).…”

Section: Orexins In Diseasementioning

confidence: 99%

Orexins as Novel Therapeutic Targets in Inflammatory and Neurodegenerative Diseases

et al. 2019

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Orexins [orexin-A (OXA) and orexin-B (OXB)] are two isoforms of neuropeptides produced by the hypothalamus. The main biological actions of orexins, focused on the central nervous system, are to control the sleep/wake process, appetite and feeding, energy homeostasis, drug addiction, and cognitive processes. These effects are mediated by two G protein-coupled receptor (GPCR) subtypes named OX1R and OX2R. In accordance with the synergic and dynamic relationship between the nervous and immune systems, orexins also have neuroprotective and immuno-regulatory (i.e., anti-inflammatory) properties. The present review gathers recent data demonstrating that orexins may have a therapeutic potential in several pathologies with an immune component including multiple sclerosis, Alzheimer's disease, narcolepsy, obesity, intestinal bowel diseases, septic shock, and cancers.

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Sepsis and the orexin system

Cited by 6 publications

References 32 publications

Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier

Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier

Plasma orexin A does not reflect severity of illness in the intensive care units patients with systemic inflammation

Orexins as Novel Therapeutic Targets in Inflammatory and Neurodegenerative Diseases

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