Inhibiting ER Stress Weakens Neuronal Pyroptosis in a Mouse Acute Hemorrhagic Stroke Model
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Inhibiting ER Stress Weakens Neuronal Pyroptosis in a Mouse Acute Hemorrhagic Stroke Model Guang Chen 1 & Cheng Gao 1 & Ya’nan Yan 1 & Tao Wang 1 & Chengliang Luo 1 & Mingyang Zhang 1 & Xiping Chen 1 & Luyang Tao 1 Received: 22 April 2020 / Accepted: 25 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Intracerebral hemorrhage . Endoplasmic reticulum stress . Pyroptosis . Interleukin-13 . Programmed cell death
Introduction Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high morbidity and mortality [1]. Although extensive clinical and experimental studies have been conducted to explore the pathophysiological mechanisms of ICH-induced cell insults and cell death, the mortality of ICH remains at 30– 50% [2] and ICH is also reportedly the only form of stroke lacking specific therapy in the present day [3]. It has been widely accepted that ICH leads to tissue displacement and Guang Chen, Cheng Gao and Ya’nan Yan contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02097-9) contains supplementary material, which is available to authorized users. * Xiping Chen [email protected] * Luyang Tao [email protected] 1
Department of Forensic Medicine, Medical School of Soochow University, 178 East Ganjiang Road, Suzhou 215213, China
destruction, which induces secondary brain injuries (SBI) [4] such as aggravation of ischemia and edema in a hematoma, accumulation of toxic by-products, excitotoxicity, oxidative stress, and inflammation. Ultimately, these pathophysiological changes lead to massive cell death, including necrosis and programmed cell death (PCD) such as apoptosis, autophagy, and pyroptosis [5
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