{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T09:22:08Z","timestamp":1769764928326,"version":"3.49.0"},"reference-count":61,"publisher":"S. Karger AG","issue":"2-3","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Hypoxia\/ischemia (HI) is a prevalent reason for neonatal brain injury with inflammation being an inevitable phenomenon following such injury; but there is a scarcity of data regarding the signaling pathway involved and the effector molecules. The signal transducer and activator of transcription factor 3 (STAT3) is known to modulate injury following imbalance between pro- and anti-inflammatory cytokines in peripheral and central nervous system injury making it a potential molecule for study. The current study investigates the temporal expression of interleukin (IL)-6, IL-1\u03b2, tumor necrosis factor-\u03b1, IL-1ra, IL-4, IL-10, IL-13 and phosphorylated STAT3 (pSTAT3) after carotid occlusion and hypoxia (8% O&lt;sub&gt;2&lt;\/sub&gt;, 55 min) in postnatal day 7 C57BL\/6 mice from 3 h to 21 days after hypoxia. Protein array illustrated notable changes in cytokines expressed in both hemispheres in a time-dependent manner. The major pro-inflammatory cytokines showing immediate changes between ipsi- and contralateral hemispheres were IL-6 and IL-1\u03b2. The anti-inflammatory cytokines IL-4 and IL-13 demonstrated a delayed augmentation with no prominent differences between hemispheres, while IL-1ra showed two distinct peaks of expression spread over time. We also illustrate for the first time the spatiotemporal activation of pSTAT3 (Y705 phosphorylation) after a neonatal HI in mice brain. The main regions expressing pSTAT3 were the hippocampus and the corpus callosum. pSTAT3+ cells were mostly a subpopulation of activated astrocytes (GFAP+) and microglia\/macrophages (F4\/80+) seen only in the ipsilateral hemisphere at most time points studied (till 7 days after hypoxia). The highest expression of pSTAT3+ cells was observed to be around 24-48 h, where the presence of pSTAT3+ astrocytes and pSTAT3+ microglia\/macrophages was seen by confocal micrographs. In conclusion, our study highlights a synchronized expression of some pro- and anti-inflammatory cytokines, especially in the long term not previously defined. It also points towards a significant role of STAT3 signaling following micro- and astrogliosis in the pathophysiology of neonatal HI-related brain injury. In the study, a shift from pro-inflammatory to anti-inflammatory cytokine profile was also noted as the injury progressed. We suggest that while designing efficient neuroprotective therapies using inflammatory molecules, the time of intervention and balance between the pro- and anti-inflammatory cytokines must be considered.<\/jats:p>","DOI":"10.1159\/000348432","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T08:35:44Z","timestamp":1365064544000},"page":"212-225","source":"Crossref","is-referenced-by-count":45,"title":["Temporal Expression of Cytokines and Signal Transducer and Activator of Transcription Factor 3 Activation after Neonatal Hypoxia\/Ischemia in Mice"],"prefix":"10.1159","volume":"35","author":[{"given":"K.","family":"Shrivastava","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Llovera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Recasens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Chertoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Gim\u00e9nez-Llort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Acarin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2013,4,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1999.tb00567.x"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60030-0"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(89)80132-5"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh618"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.110858"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041996"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01064"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112066"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.07.003"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.83"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1159\/000103741"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01811-7"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22419"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1159\/000232556"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2102-11.2011"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00035-5"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1177\/1073858406298336"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/781512"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1042\/BST0341267"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.11.024"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01378-2"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19981101)54:3<320::AID-JNR3>3.0.CO;2-R"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1594.2011.01386.x"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10498.x"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-97"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.2008.19.4-5.341"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408092200"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410090206"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb48634.x"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.10007"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00892-0"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.47.1.32"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990115)55:2<158::AID-JNR3>3.3.CO;2-T"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020562"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016\/0736-5748(94)00061-7"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(99)00187-3"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199911000-00010"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01661-1"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2005.06.006"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/561494"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1378\/chest.118.2.503"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10357"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10057"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-009-9164-4"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.593772"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.20106"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.01.010"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.04.115"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00077-2"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-240317"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7701"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04051.x"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(200005)30:3<253::AID-GLIA5>3.0.CO;2-O"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10186"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009567"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02435-06"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1023\/B:NERE.0000014830.06376.e6"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1302-06.2006"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20205"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.04.019"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03227.x"}],"container-title":["Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/348432","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/348432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:55:30Z","timestamp":1745434530000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000348432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":61,"journal-issue":{"issue":"2-3","published-online":{"date-parts":[[2013,7,1]]},"published-print":{"date-parts":[[2013,7,3]]}},"URL":"https:\/\/doi.org\/10.1159\/000348432","archive":["Portico"],"relation":{},"ISSN":["0378-5866","1421-9859"],"issn-type":[{"value":"0378-5866","type":"print"},{"value":"1421-9859","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}