Abstract
As one of the main types of secondary craniocerebral injury, the onset, progression, and prognosis of chronic subdural hematoma (CSDH) are closely related to the local inflammation of intracranial hematoma. Atorvastatin is reported to be effective in the conservative treatment of CSDH. This study aimed to clarify whether atorvastatin regulated the inflammatory responses in CSDH by interfering with the function of macrophages. The rat CSDH model was prepared by repeated intracranial blood injection with velocity gradient, and MRI was applied to calculate the intracranial hematoma volume. Changes in rat nerve functions were evaluated by foot-fault and Morris water maze tests. Flow cytometry was applied to detect the number of total macrophages and the percentage of M1 or M2 macrophages. The expression of inflammatory factors was examined by ELISA and western blot. Western bolt was applied to detect the expression of proteins involved in the colony-stimulating factor 1 receptor (CSF-1R) signaling pathway. Our results showed that atorvastatin significantly accelerated the absorption of hematoma and improved the nerve functions of CSDH rats. In addition, atorvastatin treatment effectively suppressed the expression of TNF-α, IL-6, and IL-8 and promoted the expression of IL-10. The total number of macrophages was decreased, and the percentage of M2 macrophages was increased in the intracranial hematoma following atorvastatin treatment. Furthermore, atorvastatin increased the levels of M2-related genes and surface markers in BMDMs stimulated by lipopolysaccharides and IFNγ, and activated the CSF-1R signaling pathway. In conclusion, our study shows that atorvastatin could alleviate the symptoms of CSDH and promote hematoma ablation by polarizing macrophages to M2 type and regulating the inflammatory responses.
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The study was supported by the Beijing Tianjin Hebei Basic Research Cooperation Project (19JCZDJC64600(Z)) and the National Key Research and Development Program of China (2017YFE0110400).
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Liang Yang: data curation, data analysis, drafting of the article, and final approval of the version to be published. Nan Li: data curation, data analysis, drafting of the article, and final approval of the version to be published. Lijun Yang: data curation, data analysis, drafting of the article, and final approval of the version to be published. Dong Wang: data curation, data analysis, drafting of the article, and final approval of the version to be published. Shuke Qiang: data curation, data analysis, drafting of the article, and final approval of the version to be published. Zongmao Zhao: study supervision, coordination, funding support, design of this study, drafting of the article, and final approval of the version to be published.
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Yang, L., Li, N., Yang, L. et al. Atorvastatin-Induced Absorption of Chronic Subdural Hematoma Is Partially Attributed to the Polarization of Macrophages. J Mol Neurosci 72, 565–573 (2022). https://doi.org/10.1007/s12031-021-01910-x
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DOI: https://doi.org/10.1007/s12031-021-01910-x