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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 \u201csupport cells,\u201d 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\u2010cell interactions in the context of EoP, such as the roles for border\u2010associated 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\u2010clinical 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.<\/jats:p>","DOI":"10.1002\/glia.24474","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T10:21:47Z","timestamp":1698834107000},"page":"475-503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Key roles of glial cells in the encephalopathy of prematurity"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-4856","authenticated-orcid":false,"given":"Juliette","family":"Van Steenwinckel","sequence":"first","affiliation":[{"name":"NeuroDiderot, INSERM Universit\u00e9 Paris Cit\u00e9  Paris 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