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.

脑出血（ICH）是中风的一种形式，其特点是发病率高和死亡率高，目前尚缺乏特异性疗法。ICH会导致内质网（ER）应激，该应激可通过与程序性细胞死亡（PCD）发生的串扰来诱发神经系统损伤。焦磷酸病是PCD的一种新发现形式，由于它与某些疾病（如颅脑外伤，缺血性和出血性中风）密切相关而受到关注。然而，ICH内质网应激与发烧之间的关系仍不清楚。在这项研究中，我们调查了内质网应激在诱发小鼠ICH模型中神经元凋亡和相关机制中的作用。我们使用了牛磺去氧胆酸（TUDCA）来抑制内质网应激，并观察到TUDCA减少了神经元凋亡，并具有神经保护作用。我们通过测试白介素13（IL-13）的表达，探索了通过内质网应激调节神经元凋亡的潜在机制。我们发现ER应激抑制通过降低ICH后IL-13的表达来减轻神经元的凋亡。总之，这项研究表明，IL-13与ICH后内质网应激引起的神经元细胞凋亡有关，并指出IL-13是ICH治疗的新型治疗靶点。