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Inhibiting ER Stress Weakens Neuronal Pyroptosis in a Mouse Acute Hemorrhagic Stroke Model

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Abstract

Intracerebral hemorrhage (ICH) is a form of stroke, characterized by high morbidity and mortality and currently lacks specific therapy. ICH leads to endoplasmic reticulum (ER) stress, which can induce neurological impairment through crosstalk with programmed cell death (PCD). Pyroptosis, a newly discovered form of PCD, has received attention because of its close relationship with some certain diseases, such as traumatic brain injury and ischemic and hemorrhagic stroke. However, the relationship between ER stress and pyroptosis in ICH remains unclear. In this study, we investigated the role of ER stress in evoking neuronal pyroptosis and related mechanisms in a mouse ICH model. We used tauroursodeoxycholic acid (TUDCA) to inhibit ER stress and observed that TUDCA reduces neuronal pyroptosis and has a neuroprotective role. We explored the potential mechanisms underlying the regulation of neuronal pyroptosis by ER stress through testing the expression of interleukin-13 (IL-13). We found that ER stress inhibition alleviates neuronal pyroptosis through decreasing the expression of IL-13 after ICH. In summary, this study revealed that IL-13 is involved in ER stress–induced neuronal pyroptosis after ICH, pointing to IL-13 as a novel therapeutic target for ICH treatment.

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Funding

This work was supported by the Natural Science Foundation of China (Grant no. 81530062, 81871536, and 81971800) and PAPD.

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Author notes

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

Authors and Affiliations

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

    Guang Chen, Cheng Gao, Ya’nan Yan, Tao Wang, Chengliang Luo, Mingyang Zhang, Xiping Chen & Luyang Tao

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  1. Guang Chen
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Correspondence to 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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Chen, G., Gao, C., Yan, Y. et al. Inhibiting ER Stress Weakens Neuronal Pyroptosis in a Mouse Acute Hemorrhagic Stroke Model. Mol Neurobiol 57, 5324–5335 (2020). https://doi.org/10.1007/s12035-020-02097-9

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