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Targeting astrocyte-monocyte-neuron crosstalk in spinal cord injury: therapeutic insights from methyl gallate

Spinal Cord (2025)Cite this article

Subjects

Abstract

Study design

Integrative multi-omics cross-sectional study combining scRNA-seq, bulk transcriptomics, Mendelian randomization, and network pharmacology with molecular docking.

Objective

To investigate the therapeutic mechanisms of methyl gallate (MG) in spinal cord injury (SCI) through the lens of cell-type-specific pathways and immune regulation.

Setting

Publicly available SCI transcriptomic datasets and GWAS summary data were analyzed using established bioinformatics platforms.

Methods

This study integrated single-cell RNA sequencing (scRNA-seq), transcriptomics, genome-wide association study (GWAS)-based Mendelian randomization (MR), and network pharmacology to explore MG’s effects on SCI. Temporal scRNA-seq profiles were analyzed from mice with subacute SCI (days 3 to 14 post-injury) to identify changes in astrocyte dynamics and glia-neuron interactions. Differential gene expression and functional enrichment analyses were performed, followed by drug–target prediction and molecular docking.

Results

scRNA-seq revealed a significant reduction in astrocyte populations and disrupted astrocyte–monocyte–neuron communication post-SCI. A total of 959 astrocyte-specific and 1,459 SCI-related differentially expressed genes (DEGs) were identified. Enrichment analyses highlighted neuroimmune and inflammatory pathways. MR indicated a protective association between elevated monocyte count and reduced SCI risk. Network pharmacology and molecular docking demonstrated that MG targets overlapped with astrocyte DEGs, suggesting high binding affinities and regulatory effects on inflammation and neuron–glia signaling.

Conclusions

MG may promote recovery from SCI by modulating neuroimmune interactions, particularly through astrocyte and monocyte-mediated pathways. The integrative multi-omics strategy supports MG’s translational potential as a novel therapeutic candidate for SCI.

Mechanism of SCI Repair and Neuronal Differentiation Mediated by MG (Created by BioRender).

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Fig. 1: Dynamic Changes in Astrocytes Following SCI and Their Therapeutic Potential.
Fig. 2: Exploring the Molecular Mechanisms and Therapeutic Potential of Astrocytes in SCI.
Fig. 3: MR Analysis of Monocyte Count and SCI.
Fig. 4: Network Pharmacology Analysis Exploring Key Target Genes of MG.

Data availability

The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding authors.

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Author information

Authors and Affiliations

  1. Department of Neurology, The Second Hospital of Jilin University, Changchun, 130021, China

    Xing Zhao, Hang Li, Lili Lian & Qiuru Li

  2. Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, 130021, China

    Miao Bai

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  1. Xing Zhao
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  2. Miao Bai
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  3. Hang Li
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  4. Lili Lian
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Contributions

X.Z., M.B., and H.L. contributed to the study design and data analysis. L.L. and Q.L. supervised the project and provided critical revisions to the manuscript. X.Z., L.L., and Q.L. were responsible for manuscript writing and final approval. All authors reviewed the manuscript.

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Correspondence to Lili Lian or Qiuru Li.

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This study does not involve animal or human clinical ethics. Ethical approval is not required.

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Zhao, X., Bai, M., Li, H. et al. Targeting astrocyte-monocyte-neuron crosstalk in spinal cord injury: therapeutic insights from methyl gallate. Spinal Cord (2025). https://doi.org/10.1038/s41393-025-01127-4

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