{
  "abstract": "Background Melatonin protects against ischaemic stroke in diabetic animal models, though the mechanisms involving brain and peripheral immune responses remain underexplored. We aimed to clarify how melatonin interacts with these immune responses to protect against stroke in diabetic mice.Methods Type 1 diabetes mellitus (T1DM) was induced in mice using streptozotocin. RNA sequencing of brain tissue and peripheral blood mononuclear cells (PBMCs) was performed 24 hours poststroke. Inflammatory responses were evaluated 72 hours after ischaemia/reperfusion.Results Melatonin reduced infarction and improved neurological function in T1DM mice. In the ischaemic brain, melatonin downregulated inflammatory factor expression, with bioinformatics identifying 62 differentially expressed genes (DEGs) related to inflammation and 11 associated with inflammasomes. Western blotting confirmed reductions in NLRP3, HMGB1 and Cleaved Caspase-1 expression. Flow cytometry showed reduced infiltration of CD8+T cells and neutrophils. Melatonin decreased IL-6, IL-1β and IL-4 levels. In PBMCs, RNA sequencing revealed 939 DEGs following melatonin treatment. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that downregulated DEGs were involved in metabolic pathways, and upregulated DEGs were enriched in the Jak-STAT signalling pathway. GO analysis showed that downregulated DEGs were enriched in the cytosol, and upregulated DEGs related to macromolecule modification. Protein–protein interaction analysis revealed that melatonin affected 38 inflammation-associated genes linked to key cytokines (Il6, Il1b, Ifng, Il4). Flow cytometry indicated melatonin increased CD8+T cells, monocytes and neutrophils in the blood, suggesting a reversal of immunosuppression. Multiplex cytokine assays showed melatonin decreased IL-6 and IFN-γ levels.Conclusion Poststroke melatonin therapy reduces ischaemic brain damage in T1DM mice by modulating central and peripheral inflammatory responses.",
  "authors": [
    {
      "affiliations": [
        "School of Nursing, Capital Medical University, Beijing, China"
      ],
      "name": "Cuiying Liu"
    },
    {
      "affiliations": [
        "Department of Neurobiology, School of Basic Medical Science, Capital Medical University, Beijing, China"
      ],
      "name": "Jiayi Guo"
    },
    {
      "affiliations": [
        "China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China"
      ],
      "name": "Longfei Guan"
    },
    {
      "affiliations": [
        "Department of Neurobiology, School of Basic Medical Science, Capital Medical University, Beijing, China"
      ],
      "name": "Junfa Li"
    },
    {
      "affiliations": [
        "Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "Baohui Xu"
    },
    {
      "affiliations": [
        "Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China"
      ],
      "name": "Heng Zhao"
    }
  ],
  "title": "Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation",
  "uid": "24533baf-be6e-56e3-9e5c-2f52649c8bd9"
}