Evidence mapPaperPMID 40000029Full record

ArticleStroke and vascular neurology2025

Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation.

Cuiying Liu, Jiayi Guo, Longfei Guan, Junfa Li, Baohui Xu, Heng Zhao

Abstract read
In one paragraph

Article in Stroke and vascular neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Cuiying Liu *School of Nursing, Capital Medical University, Beijing, China.ORCID 0000-0003-4162-543X
Jiayi Guo *Department of Neurobiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
Longfei GuanChina-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Junfa LiDepartment of Neurobiology, School of Basic Medical Science, Capital Medical University, Beijing, China.ORCID 0000-0002-1930-9724
Baohui XuDivision of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA.ORCID 0000-0002-2857-7464
Heng ZhaoBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China hengzhao@ccmu.edu.cn.ORCID 0009-0004-4722-5634

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMelatonin 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.

methodsType 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.

resultsMelatonin 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.

conclusionPoststroke melatonin therapy reduces ischaemic brain damage in T1DM mice by modulating central and peripheral inflammatory responses.

Indexed as

Anti-Inflammatory AgentsBrainDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Inflammation MediatorsIschemic StrokeMelatoninNeuroinflammatory DiseasesNeuroprotective AgentsAnimalsCytokinesDisease Models, AnimalHMGB1 ProteinInflammasomesLeukocytes, MononuclearMaleAnti-Inflammatory AgentsCytokinesHMGB1 ProteinHMGB1 protein, mouseInflammasomesInflammation MediatorsMelatoninNeuroprotective AgentsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseCerebral InfarctionInflammationInflammatory ResponseStroke

Identifiers

PMID40000029
PMCPMC12573409

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.