在早产儿模型中,剖腹产和全身炎症会协同破坏新生儿肠道微生物群和大脑发育。

IF 8.8 2区 医学 Q1 IMMUNOLOGY Brain, Behavior, and Immunity Pub Date : 2024-10-22 DOI:10.1016/j.bbi.2024.10.023
Cécile Morin , Flora Faure , Julie Mollet , David Guenoun , Ariane Heydari-Olya , Irvin Sautet , Sihao Diao , Valérie Faivre , Julien Pansiot , Lara Tabet , Jennifer Hua , Leslie Schwendimann , Amazigh Mokhtari , Rebeca Martin-Rosique , Sead Chadi , Mireille Laforge , Charlie Demené , Andrée Delahaye-Duriez , Rochellys Diaz-Heijtz , Bobbi Fleiss , Cindy Bokobza
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引用次数: 0

摘要

早产儿(妊娠 28 周以下)患神经发育障碍(如智力缺陷、自闭症谱系障碍和注意力缺陷)的风险很高。早产往往是在绒毛膜羊膜炎和产后败血症导致围产期全身炎症的情况下发生的。此外,为了避免阴道分娩过程中的缺氧,通常会对极早产新生儿实施剖腹产。我们开发了一种小鼠模型,并对其进行了表征,该模型基于在出生后第 1 天和第 5 天之间腹腔注射 IL-1β,以再现围产期全身炎症。该模型复制了在早产儿身上观察到的几种神经病理学、脑成像和行为缺陷。我们假设剖腹产会与全身炎症协同诱发更严重的大脑异常。我们观察到,与阴道分娩加腹腔注射生理盐水相比,剖腹产明显加剧了IL-1β对肠道微生物多样性减少、循环肽聚糖水平升高、小胶质细胞/巨噬细胞反应异常、髓鞘化受损和大脑功能连接性降低的有害影响。这些数据证明了剖腹产和新生儿全身炎症对大脑发育不良和功能失调的有害协同作用,而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。
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C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity
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.
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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