ArticleJournal of neuroinflammation2018
Activation of melanocortin receptor 4 with RO27-3225 attenuates neuroinflammation through AMPK/JNK/p38 MAPK pathway after intracerebral hemorrhage in mice.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed.
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review).International journal of molecular medicine · 2026Review
- Electroacupuncture alleviates blood-brain barrier disruption and neuroinflammation via astrocytic MC4R in a mouse model of multiple sclerosis.Journal of neuroinflammation · 2025Article
- Nutritional Modulation of the Endogenous Antioxidant System in the Brain-Gut Axis Following Traumatic Brain Injury.Nutrients · 2025Article
- Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.Diseases (Basel, Switzerland) · 2025Review
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- miR-210 Regulates Autophagy Through the AMPK/mTOR Signaling Pathway, Reduces Neuronal Cell Death and Inflammatory Responses, and Enhances Functional Recovery Following Cerebral Hemorrhage in Mice.Neurochemical research · 2025Article
- Spinal TREM2/PI3K/Akt signal axis elicits microglial activation and aggravates bone cancer pain.Journal of anesthesia and translational medicine · 2025Article
- Astaxanthin Alleviates Oxidative Stress in Mouse Preantral Follicles and Enhances Follicular Development Through the AMPK Signaling Pathway.International journal of molecular sciences · 2025Article
- Licochalcone D mitigates intracerebral hemorrhage-induced ferroptosis of neurons through COX2 inhibition.Frontiers in pharmacology · 2025Article
- Setmelanotide-mediated MC4R activation improves hypothalamic obesity via CaMKK2/AMPK pathways.Frontiers in pharmacology · 2025Article
- Resolvin D1 combined with exercise rehabilitation alleviates neurological injury in mice with intracranial hemorrhage via the BDNF/TrkB/PI3K/AKT pathway.Scientific reports · 2024Article
- Celastrol ameliorates hypoxic-ischemic brain injury in neonatal rats by reducing oxidative stress and inflammation.Pediatric research · 2024Article
- Therapeutic utility of Perfluorocarbon Oxygent in limiting the severity of subarachnoid hemorrhage in mice.Scientific reports · 2024Article
- Adiponectin deficiency is a critical factor contributing to cognitive dysfunction in obese mice after sevoflurane exposure.Molecular medicine (Cambridge, Mass.) · 2024Article
- Melanin concentrating hormone regulates the JNK/ERK signaling pathway to alleviate influenza A virus infection-induced neuroinflammation.Journal of neuroinflammation · 2024Article
- Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide.Molecular metabolism · 2024Article
- MFGE8 promotes adult hippocampal neurogenesis in rats following experimental subarachnoid hemorrhage via modifying the integrin β3/Akt signaling pathway.Cell death discovery · 2024Article
- Activating MC4R Promotes Functional Recovery by Repressing Oxidative Stress-Mediated AIM2 Activation Post-spinal Cord Injury.Molecular neurobiology · 2024Article
14 more citing papers are in PubMed but not listed here.
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9 authors.
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Abstract
backgroundNeuroinflammation plays an important role in the pathogenesis of intracerebral hemorrhage (ICH)-induced secondary brain injury. Activation of melanocortin receptor 4 (MC4R) has been shown to elicit anti-inflammatory effects in many diseases. The objective of this study was to explore the role of MC4R activation on neuroinflammation in a mouse ICH model and to investigate the contribution of adenosine monophosphate-activated protein kinase (AMPK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway in MC4R-mediated protection.
methodsAdult male CD1 mice (n = 189) were subjected to intrastriatal injection of bacterial collagenase or sham surgery. The selective MC4R agonist RO27-3225 was administered by intraperitoneal injection at 1 h after collagenase injection. The specific MC4R antagonist HS024 and selective AMPK inhibitor dorsomorphin were administered prior to RO27-3225 treatment to elucidate potential mechanism. Short- and long-term neurobehavioral assessments, brain water content, immunofluorescence staining, and western blot were performed.
resultsThe expression of MC4R and p-AMPK increased after ICH with a peak at 24 h. MC4R was expressed by microglia, neurons, and astrocytes. Activation of MC4R with RO27-3225 improved the neurobehavioral functions, decreased brain edema, and suppressed microglia/macrophage activation and neutrophil infiltration after ICH. RO27-3225 administration increased the expression of MC4R and p-AMPK while decreasing p-JNK, p-p38 MAPK, TNF-α, and IL-1β expression, which was reversed with inhibition of MC4R and AMPK.
conclusionsOur study demonstrated that activation of MC4R with RO27-3225 attenuated neuroinflammation through AMPK-dependent inhibition of JNK and p38 MAPK signaling pathway, thereby reducing brain edema and improving neurobehavioral functions after experimental ICH in mice. Therefore, the activation of MC4R with RO27-3225 may be a potential therapeutic approach for ICH management.
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