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The Notch\u2010 Delta\u2010Serrate\u2010Lag2 (DSL) signaling pathway is considered essential for the maintenance of neural stem cells, but it is not known if it is necessary for the expansion of the NSPs subsequent to perinatal H\u2010I injury. Therefore, the aim of this study was to investigate whether this pathway contributes to NSP expansion in the SVZ after H\u2010I and, if so, to establish whether this pathway is directly induced by H\u2010I or regulated by paracrine factors. Here we report that Notch1 receptor induction and one of its ligands, Delta\u2010like 1, precedes NSP expansion after perinatal H\u2010I in P6 rat pups and that this increase occurs specifically in the most medial cell layers of the SVZ where the stem cells reside. Pharmacologically inhibiting Notch signaling in vivo diminished NSP expansion. With an in vitro model of H\u2010I, Notch1 was not induced directly by hypoxia, but was stimulated by soluble factors, specifically leukemia inhibitory factor, produced by astrocytes within the SVZ. These data confirm the importance both of the Notch\u2010DSL signaling pathway in the expansion of NSPs after H\u2010I and in the role of the support cells in their niche. They further support the body of evidence that indicates that leukemia inhibitory factor is a key injury\u2010induced cytokine that is stimulating the regenerative response of the NSPs. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23929","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T15:12:49Z","timestamp":1474643569000},"page":"1531-1545","source":"Crossref","is-referenced-by-count":26,"title":["Astrocyte\u2010produced leukemia inhibitory factor expands the neural stem\/progenitor pool following perinatal hypoxia\u2013ischemia"],"prefix":"10.1002","volume":"94","author":[{"given":"Ryan J.","family":"Felling","sequence":"first","affiliation":[{"name":"Departments of Neurology and Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Department of Pharmacology, Physiology and Neuroscience RBHS\u2013New Jersey Medical School Newark New 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