Ethyl pyruvate alleviates NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis in neonatal rats with hypoxic–ischemic brain damage

IF 1.7 4区医学 Q3 DEVELOPMENTAL BIOLOGY

International Journal of Developmental Neuroscience Pub Date : 2024-06-28 DOI:10.1002/jdn.10357

Sha Sha, Ni Jin, Xinyi Xie, Ruiyu Zhou, Yanghao Ruan, Ying Ouyang

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Abstract

Pyroptosis is an inflammation-associated programmed cell death, and neuroinflammation is strongly associated with severe neurological deficits in neonatal hypoxic–ischemic encephalopathy (HIE). Ethyl pyruvate (EP), a known anti-inflammatory agent, has shown promise in the treatment of hypoxic–ischemic brain damage (HIBD) rats; nevertheless, the therapeutic mechanism of EP and its capacity to suppress neuronal pyroptosis in HIBD rats remain unclear. In both the neonatal Rice-Vannucci rat model and the OGD/R model, this study examined alterations in the NLRP3/Caspase-1/GSDMD classical pyroptosis pathway in hippocampal neurons during HIE and the potential inhibitory impact of ethyl pyruvate on this pathway. We used HE staining, immunofluorescence double staining, transmission electron microscopy, and western blot to demonstrate that EP effectively inhibited hippocampal neuronal pyroptosis and attenuated the activation of the NLRP3/Caspase-1/GSDMD signaling pathway in HIBD rats, which resulted in a reduction of neuroinflammation and facilitated neural recovery. The results suggest that EP may be a promising neuroprotective agent for treating HIE.

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丙酮酸乙酯可减轻缺氧缺血性脑损伤新生大鼠NLRP3/Caspase-1/GSDMD介导的神经元焦痂病。

烧伤是一种与炎症相关的程序性细胞死亡，而神经炎症与新生儿缺氧缺血性脑病（HIE）的严重神经功能缺损密切相关。丙酮酸乙酯（EP）是一种已知的抗炎剂，在治疗缺氧缺血性脑损伤（HIBD）大鼠方面已显示出前景；然而，丙酮酸乙酯的治疗机制及其抑制 HIBD 大鼠神经元脓毒症的能力仍不清楚。在新生 Rice-Vannucci 大鼠模型和 OGD/R 模型中，本研究考察了 HIE 期间海马神经元中 NLRP3/Caspase-1/GSDMD 经典热凋亡通路的改变以及丙酮酸乙酯对该通路的潜在抑制作用。我们采用HE染色、免疫荧光双重染色、透射电镜和Western blot等方法证明，EP能有效抑制HIBD大鼠海马神经元的热凋亡，减弱NLRP3/Caspase-1/GSDMD信号通路的激活，从而减轻神经炎症，促进神经恢复。结果表明，EP可能是一种治疗HIE的有前途的神经保护剂。

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来源期刊

International Journal of Developmental Neuroscience 医学-发育生物学

CiteScore

3.30

自引率

5.60%

发文量

审稿时长

6-12 weeks

期刊介绍： International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.