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This study integrated clinical and experimental approaches to investigate the pathological changes linking systemic inflammation to brain injury in preterm infants. Transcriptomic analysis of septic preterm infants\u2019 peripheral blood revealed upregulated immune, metabolic, and inflammatory pathways, suggesting a link between systemic and brain inflammation. Using P2 mice, we established a preterm white matter injury model through multiple doses of lipopolysaccharide, observing dose-dependent developmental delays, brain inflammation, and long-term behavioral deficits. Integrative analyses of peripheral blood and brain samples from both mice and preterm infants revealed consistent chemokine alterations and immune cell infiltration across peripheral and central compartments, highlighting the significant involvement of neutrophil extracellular traps in preterm brain injury. Furthermore, microglia exhibited significant transcriptional changes during the acute phase, accompanied by metabolic reprogramming from oxidative phosphorylation to glycolysis, with suggested involvement of Pgk1 and Pgam1. This shift intensified with escalating inflammation, along with PANoptosis-related gene upregulation, ultimately associated with microglial cell death. Collectively, these findings provide pathological insights into the immunometabolic alterations underlying sepsis-induced preterm brain injury and suggest potential targets for future therapeutic interventions to mitigate long-term neurodevelopmental deficits.<\/jats:p>","DOI":"10.1186\/s40478-025-02002-2","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T02:45:41Z","timestamp":1745203541000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Neutrophil infiltration and microglial shifts in sepsis induced preterm brain injury: pathological insights"],"prefix":"10.1186","volume":"13","author":[{"given":"Jinjin","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinnan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"2002_CR1","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1007\/s10803-010-1006-y","volume":"40","author":"HO Atlad\u00f3ttir","year":"2010","unstructured":"Atlad\u00f3ttir HO, Thorsen P, \u00d8stergaard L, Schendel DE, Lemcke S, Abdallah M et al (2010) Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. 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