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Thus, astrocytes critically influence neuronal network integrity. In hypoxia, astrocytes upregulate a transcriptional program that has been shown to boost neuroprotection in several models of neurological diseases. We investigated transgenic mice with astrocyte\u2010specific activation of the hypoxia\u2010response program by deleting the oxygen sensors, HIF prolyl\u2010hydroxylase domains 2 and 3 (Phd2\/3). We induced astrocytic Phd2\/3 deletion after onset of clinical signs in experimental autoimmune encephalomyelitis (EAE) that led to an exacerbation of the disease mediated by massive immune cell infiltration. We found that Phd2\/3\u2010ko astrocytes, though expressing a neuroprotective signature, exhibited a gradual loss of gap\u2010junctional Connexin\u201043 (Cx43), which was induced by vascular endothelial growth factor\u2010alpha (Vegf\u2010a) expression. These results provide mechanistic insights into astrocyte biology, their critical role in hypoxic states, and in chronic inflammatory CNS diseases.<\/jats:p>","DOI":"10.1002\/glia.24380","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T10:55:49Z","timestamp":1683197749000},"page":"2024-2044","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>HIF prolyl hydroxylase 2\/3<\/i> deletion disrupts astrocytic integrity and exacerbates neuroinflammation"],"prefix":"10.1002","volume":"71","author":[{"given":"Kamil Sebastian","family":"Rosiewicz","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC) Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin und Max Delbr\u00fcck Center or Molecular Medicine in the Helmholtz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakhrom","family":"Muinjonov","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC) Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin und Max Delbr\u00fcck Center or Molecular Medicine in the Helmholtz Association  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Kunz","sequence":"additional","affiliation":[{"name":"Technology Platform for Electron Microscopy Max Delbr\u00fcck Centre for Molecular Medicine in the Helmholtz Association (MDC)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Radbruch","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin.  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