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Article Open Access

Atorvastatin ameliorates chronic subdural hematomas by interrupting the ‘chronic subdural hematoma cycle’ via inhibition of the inflammatory response

  • Authors:
    • Jinqi Yan
    • Xiaohu Wang
    • Chen Liang
  • View Affiliations / Copyright

    Affiliations: Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
    Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 22
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    Published online on: November 14, 2025
       https://doi.org/10.3892/etm.2025.13017
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Abstract

Chronic subdural hematomas (CSDHs) are prevalent neurosurgical occurrences characterized by progressive hemorrhagic expansion, which is primarily mediated by persistent inflammation, angiogenesis and fibrinolytic dysregulation. Atorvastatin, a widely used lipid‑lowering agent with known anti‑inflammatory and angiogenesis‑modulating properties, has shown therapeutic potential in CSDH management. In the present study, network pharmacology and experimental validation were combined to elucidate the underlying mechanisms of atorvastatin in CSDH treatment. Potential targets were identified through database mining and Venn analysis, followed by Gene Ontology/Kyoto Encyclopedia of Genes and Genomes enrichment, protein‑protein interaction network construction and molecular docking. In vitro experiments were performed to evaluate the effects of atorvastatin on a tumor necrosis factor‑α‑induced endothelial inflammation model, including on inflammatory cytokine secretion, target gene expression, endothelial permeability and tube formation. A total of 19 candidate therapeutic targets were identified, which were predominantly involved in the inflammatory response, coagulation, fibrinolysis and angiogenesis pathways. Core targets, including matrix metalloproteinase (MMP)‑2, MMP‑9, interleukin (IL)‑6, C‑X‑C motif chemokine ligand 8/IL‑8 and serpin family E member 1, demonstrated strong binding affinities with atorvastatin via molecular docking analyses. Furthermore, functional experiments revealed that atorvastatin significantly suppressed the expression of pro‑inflammatory cytokines and adhesion molecules, mitigated endothelial barrier dysfunction, reversed the inhibitory effect of inflammation on endothelial tube formation and downregulated key pathogenic genes. Collectively, these findings suggest that atorvastatin may disrupt the ‘CSDH cycle’ by modulating critical inflammatory, angiogenic and fibrinolytic mechanisms, providing a scientific rationale for its therapeutic application in CSDH management. Further in vivo studies are warranted to validate these preliminary observations and to explore clinical translation to the clinic.
View Figures

Figure 1

Enrichment analysis of the potential
therapeutic targets of atorvastatin in treating chronic subdural
hematoma. The top 20 enriched Gene Ontology terms included (A)
biological processes, (B) cellular component and (C) molecular
function. (D) The top 20 enriched pathways from the Kyoto
Encyclopedia of Genes and Genomes analysis. (E) Network diagram of
the target genes and related pathways. (F) Protein-protein
interaction network of potential the target genes.

Figure 2

Molecular docking and functional
validation of potential therapeutic mechanisms of atorvastatin in
treating chronic subdural hematoma. (A) Degree values of the
protein nodes that correspond to target genes in the
protein-protein interaction network (values in parentheses indicate
node degrees). (B) Molecular docking results of atorvastatin with
proteins expressed by the core target genes. The anti-inflammatory
effects of atorvastatin in the endothelial cell inflammation model
were demonstrated. (C) Atorvastatin inhibited the TNF-α-induced
inflammatory response in HUVECs, as evidenced by decreased ICAM-1
and VCAM-1 levels in a dose-dependent manner. (D) Atorvastatin at a
concentration of 10 µmol/l reduced the secretion of inflammatory
cytokines; (E) downregulated the expression of inflammation-related
genes; and (F) protected against inflammation-induced endothelial
barrier dysfunction. Atorvastatin also reversed the inhibitory
effect of inflammation on endothelial tube formation. (G) Results
of tube formation assay for each group. Scale bars 500 µm. (H) The
tube counts in each group are shown. *P<0.05;
**P<0.01. ICAM-1, intercellular adhesion molecule 1;
VCAM-1, vascular cell adhesion molecule 1; MMP, matrix
metalloproteinase; IL, interleukin; CXCL-8, C-X-C motif chemokine
ligand 8; SERPINE-1, serpin family E member 1.
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Copy and paste a formatted citation
Spandidos Publications style
Yan J, Wang X and Liang C: Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response. Exp Ther Med 31: 22, 2026.
APA
Yan, J., Wang, X., & Liang, C. (2026). Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response. Experimental and Therapeutic Medicine, 31, 22. https://doi.org/10.3892/etm.2025.13017
MLA
Yan, J., Wang, X., Liang, C."Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response". Experimental and Therapeutic Medicine 31.1 (2026): 22.
Chicago
Yan, J., Wang, X., Liang, C."Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response". Experimental and Therapeutic Medicine 31, no. 1 (2026): 22. https://doi.org/10.3892/etm.2025.13017
Copy and paste a formatted citation
x
Spandidos Publications style
Yan J, Wang X and Liang C: Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response. Exp Ther Med 31: 22, 2026.
APA
Yan, J., Wang, X., & Liang, C. (2026). Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response. Experimental and Therapeutic Medicine, 31, 22. https://doi.org/10.3892/etm.2025.13017
MLA
Yan, J., Wang, X., Liang, C."Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response". Experimental and Therapeutic Medicine 31.1 (2026): 22.
Chicago
Yan, J., Wang, X., Liang, C."Atorvastatin ameliorates chronic subdural hematomas by interrupting the &lsquo;chronic subdural hematoma cycle&rsquo; via inhibition of the inflammatory response". Experimental and Therapeutic Medicine 31, no. 1 (2026): 22. https://doi.org/10.3892/etm.2025.13017
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