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Interleukin-13 Affects the Recovery Processes in a Mouse Model of Hemorrhagic Stroke with Bilateral Tibial Fracture

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Abstract

As one form of stroke, intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease, which has high morbidity and mortality and lacks effective medical treatment. Increased infiltration of inflammatory cytokines coupled with pyroptotic cell death is involved in the pathophysiological process of ICH. However, little is known about whether concomitant fracture patients have the same progression of inflammation and pyroptosis. Hence, we respectively established the mouse ICH model and ICH with bilateral tibial fracture model (MI) to explore the potential cross-talk between the above two injuries. We found that MI obviously reversed the expressions of pyroptosis-associated proteins, which were remarkably up-regulated at the acute phase after ICH. Similar results were observed in neuronal expressions via double immunostaining. Furthermore, brain edema was also significantly alleviated in mice who suffered MI, when compared with ICH alone. To better clarify the potential mechanisms that mediated this cross-talk, recombinant mouse interleukin-13 (IL-13) was used to investigate its effect on pyroptosis in the mouse MI model, in which a lower level of IL-13 was observed. Remarkably, IL-13 administration re-awakened cell death, which was mirrored by the re-upregulation of pyroptosis-associated proteins and PI-positive cell counts. The results of hemorrhage volume and behavioral tests further confirmed its critical role in regulating neurological functions. Besides, the IL-13-treated MI group showed poor outcomes of fracture healing. To sum up, our research indicates that controlling the IL-13 content in the acute phase would be a promising target in influencing the outcomes of brain injury and fracture, and meanwhile, provides new evidence in repairing compound injuries in clinics.

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Data Availability

All data included in this study are available upon request by contact with the corresponding author.

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Funding

This research was supported by the Natural Science Foundation of China (Grant Number: 81971800, 81871536, 82072110, and 82101452), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. Ya’nan Yan, Cheng Gao, and Guang Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Forensic Medicine, Medical School of Soochow University, 178 East Ganjiang Road, Suzhou, 215213, Jiangsu, China

    Cheng Gao, Guang Chen, Xueshi Chen, Heng Xu, Zhiqi Cheng, Chengliang Luo, Mingyang Zhang, Tao Wang, Xiping Chen & Luyang Tao

  2. Department of Forensic Medicine, School of Basic Medical Sciences, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, 341000, Jiangxi, China

    Ya’nan Yan

  3. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China

    Yanglin Wu & Jun Lin

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  1. Ya’nan Yan
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Contributions

Y.Y., C.G., and G.C. contributed equally to this paper. L.T., X.C., and J.L. comprehended the study, provided critical suggestions, contributed to manuscript preparation, oversaw the research program, and wrote the main manuscript. Y.Y., C.G., and G.C. performed the Western blot and immunostaining experiments and analyzed the data. Y.Y., C.G., G.C., X.C., H.X., Z.C., C.L., M.Z., and T.W. performed the brain edema test, PI staining, bleeding volume test, ELISA test, behavioral experiment, and analyzed the data. Y.W. performed tibial fracture surgery, micro-CT scan, and analyzed the data. All the authors listed in the manuscript have agreed upon and reviewed the manuscript and provided feedback.

Corresponding authors

Correspondence to Jun Lin, Xiping Chen or Luyang Tao.

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All animal procedures were approved by the Institutional Animal Use and Care Committee at Soochow University and carried out in accordance with the guidelines of Animal Use and Care of the National Institutes of Health (NIH) and the Animal Research: Reporting in Vivo Experiments (ARRIVE).

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Yan, Y., Gao, C., Chen, G. et al. Interleukin-13 Affects the Recovery Processes in a Mouse Model of Hemorrhagic Stroke with Bilateral Tibial Fracture. Mol Neurobiol 59, 3040–3051 (2022). https://doi.org/10.1007/s12035-021-02650-0

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