IL-33 exerts neuroprotective effects through activation of ST2/AKT signaling axis in microglia after subarachnoid hemorrhage in rats

IF 4.6 2区医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2025-02-11 DOI:10.1016/j.neuropharm.2025.110336

Ting Chen , Jiarui Chen , Mengchen Guo , Yibo Liu , Junjie Wang , Yuanjian Fang , Yan Chen , Anke Zhang

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Abstract

Background and purpose

ST2, a member of the interleukin-1 (IL-1) receptor family, along with its ligand IL-33, plays critical roles in immune regulation and inflammatory responses. This study investigates the roles of endogenous IL-33/ST2 signaling in subarachnoid hemorrhage (SAH) and elucidates the underlying mechanisms.

Methods

Dynamic changes in endogenous IL-33 levels were examined following SAH induction in vivo. Rats underwent the endovascular perforation model of SAH and were randomly assigned to receive either recombinant IL-33 (rIL-33) or a vehicle, administered intranasally 1 h post-SAH. ST2 siRNA or an AKT selective inhibitor was administered intraperitoneally (i.p.) 48 h prior to SAH induction to explore the potential mechanisms of IL-33-mediated neuroprotection.

Results

Endogenous IL-33 and ST2 levels were elevated in in vitro models of SAH. Exogenous IL-33 significantly alleviated neuronal apoptosis, reduced brain edema, and enhanced short-term neurofunction in a dose-dependent manner following SAH in rats.

Conclusion

Exogenous rIL-33 alleviates SAH-induced neurological deficits by promoting M2-like polarization of microglia post-SAH. These findings suggest a potential role of the microglial ST2/AKT axis in IL-33-related neuroprotection, which warrants further investigation.

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IL-33通过激活大鼠蛛网膜下腔出血后小胶质细胞ST2/AKT信号轴发挥神经保护作用

背景与目的st2是白细胞介素-1 （IL-1）受体家族的一员，其配体IL-33在免疫调节和炎症反应中起重要作用。本研究探讨内源性IL-33/ST2信号在蛛网膜下腔出血（SAH）中的作用，并阐明其潜在机制。方法观察体内SAH诱导后内源性IL-33水平的动态变化。大鼠采用SAH血管内穿孔模型，在SAH后1小时，随机分配接受重组IL-33 （IL-33）或载体。在SAH诱导前48小时腹腔注射ST2 siRNA或AKT选择性抑制剂，以探索il -33介导的神经保护的潜在机制。结果SAH体外模型外周血IL-33和ST2水平升高。外源性IL-33显著减轻大鼠SAH后神经元凋亡，减少脑水肿，并以剂量依赖性方式增强短期神经功能。结论外源性rIL-33通过促进sah后小胶质细胞的m2样极化来减轻sah所致的神经功能缺损。这些发现提示小胶质细胞ST2/AKT轴在il -33相关的神经保护中具有潜在作用，值得进一步研究。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).