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Integr. Neurosci."],"abstract":"<jats:p>Background: Cardiac arrest (CA) is a widespread public health problem with high mortality, severe neurological sequelae, and limited pharmacological therapies. We investigated the neuroprotective effect of a novel drug, FPS-ZM1 (FPS), on CA and explored its potential mechanism. Methods: A potassium chloride\u2013induced CA was induced for 9.5 min in mice, with i.p. injections of FPS or vehicle administered 24 and 1 h before induction. Postoperative assessments included survival rate, body weight change, neurological scores, and neuronal pathological damage. The expression levels of the high mobility group box 1 (HMGB1)\/receptor for advanced glycation end products (RAGE) axis, pyroptosis-related molecules, oxidative stress markers, and the nuclear factor erythroid 2-related factor 2 (Nrf2)\/heme oxygenase-1 (HO-1) axis were evaluated. Results: Post-CA brain injury (PCABI) activated the HMGB1\/RAGE axis, triggering intensified oxidative stress and aggravated pyroptosis. In contrast, pretreatment with FPS attenuated CA-induced injuries. FPS pretreatment was found to suppress the activation of the HMGB1\/RAGE axis, alleviate pyroptosis and the release of associated inflammatory mediators, and enhance the Nrf2\/HO-1 antioxidant axis after PCABI. Conclusion: FPS pretreatment mitigated PCABI by concurrently modulating the HMGB1\/RAGE inflammatory axis and the Nrf2\/HO-1 antioxidant pathway, suggesting that RAGE antagonism represents a promising therapeutic strategy for PCABI.<\/jats:p>","DOI":"10.31083\/jin50023","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:26:43Z","timestamp":1777451203000},"source":"Crossref","is-referenced-by-count":0,"title":["FPS-ZM1 Exerts Neuroprotection in Cardiac-Arrest Mice through Inhibiting Oxidative Stress and Pyroptosis via the HMGB1\/RAGE Axis"],"prefix":"10.31083","volume":"25","author":[{"given":"Ying","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"},{"name":"Central Laboratory, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianhui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"},{"name":"Central Laboratory, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"},{"name":"Central Laboratory, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"},{"name":"Central Laboratory, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"},{"name":"Central Laboratory, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"},{"name":"Central Laboratory, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"},{"name":"Central Laboratory, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8223-8466","authenticated-orcid":true,"given":"Zhui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Narayan SM, Wang PJ, Daubert JP. 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