NeuroDiderot, INSERM, Université Paris Cité, Paris, France.
School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Victoria, Australia.
Glia. 2024 Mar;72(3):475-503. doi: 10.1002/glia.24474. Epub 2023 Nov 1.
Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases their risk for developing lifelong defects in motor skills and domains of learning, memory, emotional regulation, and cognition. We are still severely limited in our abilities to prevent or predict preterm birth. No longer just the "support cells," we now clearly understand that during development glia are key for building a healthy brain. Glial dysfunction is a hallmark of EoP, notably, microgliosis, astrogliosis, and oligodendrocyte injury. Our knowledge of glial biology during development is exponentially expanding but hasn't developed sufficiently for development of effective neuroregenerative therapies. This review summarizes the current state of knowledge for the roles of glia in infants with EoP and its animal models, and a description of known glial-cell interactions in the context of EoP, such as the roles for border-associated macrophages. The field of perinatal medicine is relatively small but has worked passionately to improve our understanding of the etiology of EoP coupled with detailed mechanistic studies of pre-clinical and human cohorts. A primary finding from this review is that expanding our collaborations with computational biologists, working together to understand the complexity of glial subtypes, glial maturation, and the impacts of EoP in the short and long term will be key to the design of therapies that improve outcomes.
在全球范围内，大约每 10 个婴儿中就有 1 个是早产儿，也就是说，他们在妊娠 40 周的典型时间之前就出生了。多达 50%的早产儿会出现脑损伤，即早产儿脑病（EoP），这大大增加了他们在运动技能和学习、记忆、情绪调节和认知等领域发展终身缺陷的风险。我们仍然严重缺乏预防或预测早产的能力。现在我们清楚地认识到，胶质细胞不再仅仅是“支持细胞”，在发育过程中，胶质细胞对于构建健康的大脑至关重要。神经胶质功能障碍是 EoP 的一个标志，特别是小胶质细胞增生、星形胶质细胞增生和少突胶质细胞损伤。我们对发育过程中神经胶质生物学的了解正在呈指数级增长，但还没有发展到足以开发有效的神经再生疗法的程度。这篇综述总结了目前关于 EoP 婴儿及其动物模型中胶质细胞作用的知识状况，以及已知的胶质细胞相互作用在 EoP 背景下的描述，例如边界相关巨噬细胞的作用。围产医学领域相对较小，但一直在努力增进我们对 EoP 病因的理解，并结合对临床前和人类队列的详细机制研究。从这篇综述中得出的一个主要发现是，扩大我们与计算生物学家的合作，共同努力理解神经胶质亚型、神经胶质成熟的复杂性，以及 EoP 在短期和长期的影响，将是设计改善治疗结果的疗法的关键。
