Morin Cécile, Faure Flora, Mollet Julie, Guenoun David, Heydari-Olya Ariane, Sautet Irvin, Diao Sihao, Faivre Valérie, Pansiot Julien, Tabet Lara, Hua Jennifer, Schwendimann Leslie, Mokhtari Amazigh, Martin-Rosique Rebeca, Chadi Sead, Laforge Mireille, Demené Charlie, Delahaye-Duriez Andrée, Diaz-Heijtz Rochellys, Fleiss Bobbi, Matrot Boris, Auger Sandrine, Tanter Mickael, Van Steenwinckel Juliette, Gressens Pierre, Bokobza Cindy
Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France; Department of Obstetrics and Gynecology, AP-HP, Robert Debré Hospital, 75019 Paris, France.
Physics for Medicine Paris, Inserm, ESPCI Paris-PSL, CNRS, 75015 Paris, France.
Brain Behav Immun. 2025 Jan;123:824-837. doi: 10.1016/j.bbi.2024.10.023. Epub 2024 Oct 22.
Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.
极早产儿（妊娠不足28周）患神经发育障碍的风险很高，如智力缺陷、自闭症谱系障碍和注意力缺陷。早产通常发生在因绒毛膜羊膜炎导致的围产期全身炎症和产后败血症的背景下。此外，极早产新生儿常进行剖宫产以避免阴道分娩时缺氧。我们开发并表征了一种小鼠模型，该模型基于在出生后第1天至第5天腹腔注射白细胞介素-1β来模拟围产期全身炎症。该模型复制了早产儿中观察到的几种神经病理学、脑成像和行为缺陷。我们假设剖宫产可能与全身炎症协同作用，导致更严重的脑异常。我们观察到，与阴道分娩加腹腔注射生理盐水相比，剖宫产显著加剧了白细胞介素-1β对肠道微生物多样性降低、循环肽聚糖水平升高、小胶质细胞/巨噬细胞反应异常、髓鞘形成受损和脑功能连接减少的有害影响。这些数据证明了剖宫产和新生儿全身炎症对脑发育不良和功能障碍的有害协同作用，这两种情况在极早产儿中经常出现，他们患神经发育障碍的风险很高。
