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Hypoxia\u2010ischaemia (<jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>) strongly up\u2010regulates Signal Transducer and Activator of Transcription 3 (<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3) in the immature brain. Our aim was to establish whether <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 up\u2010regulation is associated with neonatal <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\u2010brain damage and evaluate the phosphorylated <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3\u2010contribution from different cell types in eliciting damage. We subjected postnatal day seven mice to unilateral carotid artery ligation followed by 60\u00a0min hypoxia. Neuronal <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3\u2010deletion reduced cell death, tissue loss, microglial and astroglial activation in all brain regions. Astroglia\u2010specific <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3\u2010deletion also reduced cell death, tissue loss and microglial activation, although not as strongly as the deletion in neurons. Systemic pre\u2010insult <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3\u2010blockade at tyrosine 705 (Y705) with <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>2\u2010inhibitor <jats:styled-content style=\"fixed-case\">WP<\/jats:styled-content>1066 reduced microglial and astroglial activation to a more moderate degree, but in a pattern similar to the one produced by the cell\u2010specific deletions. Our results suggest that <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 is a crucial factor in neonatal <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>\u2010brain damage and its removal in neurons or astrocytes, and, to some extent, inhibition of its phosphorylation via <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>2\u2010blockade reduces inflammation and tissue loss. Overall, the protective effects of <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 inactivation make it a possible target for a therapeutic strategy in neonatal <jats:styled-content style=\"fixed-case\">HI<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13490-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nCurrent data show that neuronal and astroglial <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 molecules are involved in the pathways underlying cell death, tissue loss and gliosis following neonatal hypoxia\u2010ischaemia, but differ with respect to the target of their effect. Y705\u2010phosphorylation contributes to hypoxic\u2010ischaemic histopathology. Protective effects of <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>3 inactivation make it a possible target for a therapeutic strategy in neonatal hypoxia\u2010ischaemia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13490","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T16:44:22Z","timestamp":1450197862000},"page":"981-994","source":"Crossref","is-referenced-by-count":70,"title":["Inhibition of Signal Transducer and Activator of Transcription 3 (<scp>STAT<\/scp>3) reduces neonatal hypoxic\u2010ischaemic brain damage"],"prefix":"10.1111","volume":"136","author":[{"given":"Mariya","family":"Hristova","sequence":"first","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eridan","family":"Rocha\u2010Ferreira","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Fontana","sequence":"additional","affiliation":[{"name":"Cell Growth and Regeneration Lab MRC Laboratory for Molecular Cell Biology University College London WC1E 6BT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Thei","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rheanan","family":"Buckle","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Christou","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supanida","family":"Hompoonsup","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Gostelow","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennadij","family":"Raivich","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Peebles","sequence":"additional","affiliation":[{"name":"UCL Institute for Women's Health Maternal &amp; Fetal Medicine Perinatal Brain Repair Group London WC1E 6HX UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2009.04911.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0736-5748(94)00061-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10061"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/846716"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.09.017"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1558\u201007.2007"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2102\u201011.2011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02435\u201006"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01647.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu034"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1709\u201008.2008"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.255604"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"26494","DOI":"10.1016\/S0021-9258(19)74341-5","article-title":"The 5'\u2010flanking region of the rat synapsin I gene directs neuron\u2010specific and developmentally regulated reporter gene expression in transgenic mice","volume":"268","author":"Hoesche C.","year":"1993","journal-title":"J. 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