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Ethyl pyruvate (EP), a known anti\u2010inflammatory agent, has shown promise in the treatment of hypoxic\u2013ischemic 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\u2010Vannucci rat model and the OGD\/R model, this study examined alterations in the NLRP3\/Caspase\u20101\/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\u20101\/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.<\/jats:p>","DOI":"10.1002\/jdn.10357","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T10:20:10Z","timestamp":1719570010000},"page":"594-604","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ethyl pyruvate alleviates NLRP3\/Caspase\u20101\/GSDMD\u2010mediated neuronal pyroptosis in neonatal rats with hypoxic\u2013ischemic brain damage"],"prefix":"10.1002","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4078-3084","authenticated-orcid":false,"given":"Sha","family":"Sha","sequence":"first","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Jin","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen 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