{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:45:53Z","timestamp":1790948753380,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071687"],"award-info":[{"award-number":["82071687"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>The mechanism of long-term cognitive impairment after neonatal sepsis remains poorly understood, although long-lasting neuroinflammation has been considered the primary contributor. Necroptosis is actively involved in the inflammatory process, and in this study, we aimed to determine whether neonatal sepsis-induced long-term cognitive impairment was associated with activation of necroptosis. Rat pups on postnatal day 3 (P3) received intraperitoneal injections of lipopolysaccharide (LPS, 1 mg\/kg) to induce neonatal sepsis. Intracerebroventricular injection of IL-1\u03b2-siRNA and necrostatin-1 (NEC1) were performed to block the production of IL-1\u03b2 and activation of necroptosis in the brain, respectively. The Morris water maze task and fear conditioning test were performed on P28\u2013P32 and P34\u2013P35, respectively. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-PCR), and Western blotting were used to examine the expression levels of proinflammatory cytokines and necroptosis-associated proteins, such as receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Sustained elevation of IL-1\u03b2 level was observed in the brain after initial neonatal sepsis, which would last for at least 32 days. Sustained necroptosis activation was also observed in the brain. Knockdown of IL-1\u03b2 expression in the brain alleviated necroptosis and improved long-term cognitive function. Direct inhibition of necroptosis also improved neurodevelopment and cognitive performance. This research indicated that sustained activation of necroptosis via IL-1\u03b2 contributed to long-term cognitive dysfunction after neonatal sepsis.<\/jats:p>","DOI":"10.3390\/ijms241914693","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:55:54Z","timestamp":1695880554000},"page":"14693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Involvement of IL-1\u03b2-Mediated Necroptosis in Neurodevelopment Impairment after Neonatal Sepsis in Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6950-8441","authenticated-orcid":false,"given":"Zhimin","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-7465","authenticated-orcid":false,"given":"Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9022-5873","authenticated-orcid":false,"given":"Han","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/S0140-6736(17)31002-4","article-title":"Neonatal sepsis","volume":"390","author":"Shane","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kurul, \u015e., Beckers, F.L.M., Vermeulen, M.J., Suurland, J., Hasbek, J.E., Ramakers, C.R.B., Simons, S.H.P., Reiss, I.K.M., and Taal, H.R. 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