ArticleCNS neuroscience & therapeutics2024
Orexin-A Attenuates the Inflammatory Response in Sepsis-Associated Encephalopathy by Modulating Oxidative Stress and Inhibiting the ERK/NF-κB Signaling Pathway in Microglia and Astrocytes.
Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- TREM2 Attenuates Microglial Pyroptosis in Sepsis-Associated Encephalopathy Through Modulation of the mtDNA-cGAS-STING Pathway.Molecular neurobiology · 2026Article
- Salidroside alleviates sepsis-associated acute lung injury through modulation of the ERK/FoxO3a signaling axis and improvement of impaired autophagic flux.Molecular biology reports · 2026Article
- miR-125b Attenuates Sepsis-Induced Hippocampal Mitochondrial Fission and Cognitive Impairment via the ROS/p53 Pathway.Molecular neurobiology · 2026Article
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Neuroimmune Mechanisms Transforming Acute Injury to Long-Term Brain Dysfunction After Sepsis.Clinics in chest medicine · 2026Review
- INPP5D Upregulation by Minocycline Mitigates Sepsis-Associated Neuroinflammation and Neuronal Dysfunction Via Microglial Autophagy and Antioxidant Pathways.Inflammation · 2026Article
- Astrocytes in Parkinson's Disease: From Guardians to Accomplices.Clinical interventions in aging · 2026Review
- Gut microbiota dysbiosis in sepsis and sepsis-associated organ injury: mechanisms, gut-organ axes, and therapeutic strategies.Frontiers in microbiology · 2026Review
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- Glial Cells as Central Players in Neuroinflammation and Neuronal Damage Caused by Bacterial Pneumonia.Neuroimmunomodulation · 2026Review
- Orexin-A Mitigates Traumatic Brain Injury by Inhibiting Neuronal Ferroptosis Through Orexin Receptor 1/Nuclear Factor Erythroid 2-Related Factor 2 Signaling Pathway.Molecular neurobiology · 2025Article
- Central neuropeptides as key modulators of astrocyte function in neurodegenerative and neuropsychiatric disorders.Psychopharmacology · 2025Review
- Loss of M1 Acetylcholine Receptor-mediated Orexinergic Activity Contributes to Immune Dysfunction in Experimental Sepsis.Research square · 2025Article
- Orexin/Hypocretin Modulates Neuroinflammatory Response to LPS in a Sex and Brain-Region Specific Manner in Young Rats.Journal of neurochemistry · 2025Article
- Neuropsychiatric symptoms in the context of hemodynamic disruption during septic shock.World journal of psychiatry · 2025Article
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16 authors.
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Abstract
backgroundOxidative stress-induced inflammation is a major pathogenic mechanism in sepsis-associated encephalopathy (SAE). We hypothesized that regulation of reactive oxygen species (ROS) by the neuropeptide orexin-A could prevent SAE-induced oxidative stress and inflammation. Therefore, the aim of this study was to investigate the effects of orexin-A on oxidative stress and inflammation in SAE in mice.
methodsAdult male mice were treated with orexin-A (250 μg/kg, intranasal administration) to establish a cecal ligation perforation (CLP) model. We performed behavioral tests, observed neuronal damage in the hippocampal region, measured the levels of ROS, NOX2, and observed the structure of mitochondria by transmission electron microscopy. We then examined the inflammatory factors TNF-α and IL-1β, the activation of microglia and astrocytes, the expression of ERK/NF-κB, C3, and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes.
resultsOrexin-A treatment improved cognitive performance in CLP-induced SAE mice, attenuated neuronal apoptosis in the hippocampal region, ameliorated ROS levels and the extent of mitochondrial damage, and reduced protein expression of NOX2 in hippocampal tissue. In addition, orexin-A treatment significantly reduced microglia and astrocyte activation, inhibited the levels of P-ERK and NF-κB, and reduced the release of IL-1β and TNF-α, which were significantly increased after CLP. Finally, Orexin-A treatment significantly decreased the number of C3/glial fibrillary acidic protein (GFAP)-positive cells and increased the number of S100A10/GFAP-positive cells.
conclusionOur data suggest that orexin-A reduces ROS expression by inhibiting CLP-induced NOX2 production, thereby attenuating mitochondrial damage and neuronal apoptosis. Its inhibition of microglial and A1-type astrocyte activation and inflammation was associated with the ERK/NF-κB pathway. These suggest that orexin-A may reduce cognitive impairment in SAE by reducing oxidative stress-induced inflammation.
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