ArticleJournal of neuroinflammation2020
Orexin A alleviates neuroinflammation via OXR2/CaMKKβ/AMPK signaling pathway after ICH in mice.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder.Annals of medicine · 2026Article
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- Awakening Recovery: Enhancing Orexinergic Tone After Acute CNS Damage.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Central neuropeptides as key modulators of astrocyte function in neurodegenerative and neuropsychiatric disorders.Psychopharmacology · 2025Review
- ROS-responsive 3D biological scaffold delivers hypoxia-primed extracellular vesicles for targeted modulation of neuroinflammation in intracerebral hemorrhage.Stem cell research & therapy · 2025Article
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- The clinical value of triglyceride to high-density lipoprotein cholesterol ratio for predicting stroke-associated pneumonia after spontaneous intracerebral hemorrhage.BMC neurology · 2025Article
- Sphk1/S1P pathway promotes blood-brain barrier breakdown after intracerebral hemorrhage through inducing Nlrp3-mediated endothelial cell pyroptosis.Cell death & disease · 2024Article
- Betulin ameliorates neuronal apoptosis and oxidative injury via DJ-1/Akt/Nrf2 signaling pathway after subarachnoid hemorrhage.CNS neuroscience & therapeutics · 2024Article
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- Therapeutic effects of orexin-A in sepsis-associated encephalopathy in mice.Journal of neuroinflammation · 2024Article
- Visfatin Affects the Transcriptome of Porcine Luteal Cells during Early Pregnancy.International journal of molecular sciences · 2024Article
- Receptors on Microglia.Advances in neurobiology · 2024Review
- GPNMB Ameliorates Neuroinflammation Via the Modulation of AMPK/NFκB Signaling Pathway After SAH in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- A molecular network map of orexin-orexin receptor signaling system.Journal of cell communication and signaling · 2023Article
- Blast Exposure Induces Acute Alterations in Circadian Clock Genes in the Hypothalamus and Pineal Gland in Rats: An Exploratory Study.Neurotrauma reports · 2023Article
- Chaihu-Longgu-Muli decoction improves sleep disorders by restoring orexin-A function in CKD mice.Frontiers in endocrinology · 2023Article
- Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury.Journal of clinical medicine · 2022Article
- Molecular Mechanisms Underlying CaInternational journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundOrexins are two neuropeptides (orexin A, OXA; orexin B, OXB) secreted mainly from the lateral hypothalamus, which exert a wide range of physiological effects by activating two types of receptors (orexin receptor 1, OXR1; orexin receptor 2, OXR2). OXA has equal affinity for OXR1 and OXR2, whereas OXB binds preferentially to OXR2. OXA rapidly crosses the blood-brain barrier by simple diffusion. Many studies have reported OXA's protective effect on neurological diseases via regulating inflammatory response which is also a fundamental pathological process in intracerebral hemorrhage (ICH). However, neuroprotective mechanisms of OXA have not been explored in ICH.
methodsICH models were established using stereotactic injection of autologous arterial blood into the right basal ganglia of male CD-1 mice. Exogenous OXA was administered intranasally; CaMKKβ inhibitor (STO-609), OXR1 antagonist (SB-334867), and OXR2 antagonist (JNJ-10397049) were administered intraperitoneally. Neurobehavioral tests, hematoma volume, and brain water content were evaluated after ICH. Western blot and ELISA were utilized to evaluate downstream mechanisms.
resultsOXA, OXR1, and OXR2 were expressed moderately in microglia and astrocytes and abundantly in neurons. Expression of OXA decreased whereas OXR1 and OXR2 increased after ICH. OXA treatment significantly improved not only short-term but also long-term neurofunctional outcomes and reduced brain edema in ipsilateral hemisphere. OXA administration upregulated p-CaMKKβ, p-AMPK, and anti-inflammatory cytokines while downregulated p-NFκB and pro-inflammatory cytokines after ICH; this effect was reversed by STO-609 or JNJ-10397049 but not SB-334867.
conclusionsOXA improved neurofunctional outcomes and mitigated brain edema after ICH, possibly through alleviating neuroinflammation via OXR2/CaMKKβ/AMPK pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.