{"title":"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。","authors":"Sha Sha, Ni Jin, Xinyi Xie, Ruiyu Zhou, Yanghao Ruan, Ying Ouyang","doi":"10.1002/jdn.10357","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"84 6","pages":"594-604"},"PeriodicalIF":1.7000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ethyl pyruvate alleviates NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis in neonatal rats with hypoxic–ischemic brain damage\",\"authors\":\"Sha Sha, Ni Jin, Xinyi Xie, Ruiyu Zhou, Yanghao Ruan, Ying Ouyang\",\"doi\":\"10.1002/jdn.10357\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":13914,\"journal\":{\"name\":\"International Journal of Developmental Neuroscience\",\"volume\":\"84 6\",\"pages\":\"594-604\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-06-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Developmental Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jdn.10357\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Developmental Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jdn.10357","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
Ethyl pyruvate alleviates NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis in neonatal rats with hypoxic–ischemic brain damage
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.
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.