{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:08:15Z","timestamp":1788786495804,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"crossref","award":["INV-002321"],"award-info":[{"award-number":["INV-002321"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"award":["INV-002321"],"award-info":[{"award-number":["INV-002321"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neonatal hypoxic\u2013ischemic encephalopathy (HIE) is a major cause of neonatal mortality and long-term neurological disability, affecting 1\u20133 per 1000 live births in developed countries and occurring at substantially higher rates in developing countries. Neuroinflammation is a key contributor to disease progression, with growing evidence implicating the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome following hypoxic\u2013ischemic (HI) injury. In this study, we investigated the role and regulation of the NLRP3 inflammasome in neonatal HIE using in vitro and in vivo models. Primary microglial cultures subjected to oxygen\u2013glucose deprivation and the Vannucci neonatal rat model of HI were used to characterize NLRP3 activation and its contribution to injury. We demonstrated that HI induces NLRP3 inflammasome activation, whereas pharmacological inhibition of NLRP3 enhances cell viability and attenuates brain damage. Our findings identify microglia as a central mediator of NLRP3-driven neuroinflammation and highlight microglial NLRP3 signaling as a promising therapeutic target for neuroinflammatory diseases. Collectively, this study provides an integrated view of NLRP3 regulation in neonatal HIE and supports inflammasome-directed strategies for neuroprotection following neonatal HI injury.<\/jats:p>","DOI":"10.3390\/ijms27177853","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:57:23Z","timestamp":1788346643000},"page":"7853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NLRP3 Regulation in Neonatal Hypoxic\u2013Ischemic Encephalopathy\u2014Focus on Microglial Activation"],"prefix":"10.3390","volume":"27","author":[{"given":"Hannah","family":"Burkard","sequence":"first","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care Medicine, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Maria Eugenia","family":"Bernis","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care Medicine, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Anna-Sophie","family":"Bremer","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care Medicine, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Elke","family":"Maes","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care Medicine, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Jonas","family":"Walter","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity, Biomedical Center, University Hospital Bonn, BMZ 2, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Felix","family":"Meissner","sequence":"additional","affiliation":[{"name":"Institute of Innate Immunity, Biomedical Center, University Hospital Bonn, BMZ 2, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Hemmen","family":"Sabir","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Pediatric Intensive Care Medicine, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1203\/00006450-199004000-00001","article-title":"Experimental biology of cerebral hypoxia-ischemia: Relation to perinatal brain damage","volume":"27","author":"Vannucci","year":"1990","journal-title":"Pediatr. 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