{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T16:40:49Z","timestamp":1761237649399},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            Nuclear factor-\u03baB (NF-\u03baB) is an important regulator of inflammation and apoptosis. We showed previously that NF-\u03baB inhibition by intraperitoneal TAT-NBD treatment strongly reduced neonatal hypoxic\u2013ischemic (HI) brain damage. Neuroprotection by TAT-NBD was not associated with inhibition of cerebral cytokine production. We investigated how tumor necrosis factor-\u03b1 (TNF-\u03b1) production is maintained after NF-\u03baB inhibition and whether TNF-\u03b1 contributes to brain damage.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            Postnatal Day 7 rats were subjected to unilateral carotid artery occlusion and hypoxia. Rats were treated immediately after HI with TAT-NBD, the JNK inhibitor TAT-JBD, and\/or the TNF-\u03b1 inhibitor etanercept. We determined brain damage, NF-\u03baB and AP-1 activity, Gadd45\u03b2, XIAP, (P-)TAK1, TNF-\u03b1, and TNF receptor expression.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Our data confirm that TAT-NBD treatment reduces brain damage without inhibiting TNF-\u03b1 production. We now show that TAT-NBD treatment increased HI-induced AP-1 activation concomitantly with reduced Gadd45\u03b2, XIAP, and increased (P)-TAK1 expression. Combined inhibition of NF-\u03baB and JNK\/AP-1 abrogated HI-induced TNF-\u03b1 production. However, this treatment reduced the neuroprotective effect of NF-\u03baB inhibition alone. We show that etanercept was detectable in the HI brain after intraperitoneal administration and that etanercept treatment also reduced the neuroprotective effect of NF-\u03baB inhibition. Finally, NF-\u03baB inhibition decreased HI-induced upregulation of TNF-R1 and increased TNF-R2 expression.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            When NF-\u03baB was inhibited after neonatal cerebral HI, JNK\/AP-1 activity was increased and required for increased TNF-\u03b1 expression. Our data indicate that the switch to JNK\/AP-1 activation preserves HI-induced TNF-\u03b1 expression and thereby might contribute to the neuroprotective effect of TAT-NBD possibly through a TNF-R2 dependent mechanism.\n          <\/jats:p>","DOI":"10.1161\/strokeaha.109.560250","type":"journal-article","created":{"date-parts":[[2009,7,24]],"date-time":"2009-07-24T02:06:05Z","timestamp":1248401165000},"page":"3362-3368","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Alternate Pathways Preserve Tumor Necrosis Factor-\u03b1 Production After Nuclear Factor-\u03baB Inhibition in Neonatal Cerebral Hypoxia\u2013Ischemia"],"prefix":"10.1161","volume":"40","author":[{"given":"Cora H.","family":"Nijboer","sequence":"first","affiliation":[{"name":"From the Laboratory of Psychoneuroimmunology (C.H.N., C.J.H., A.K.) and the Department of Neonatology (F.G., F.v.B.), University Medical Center Utrecht, Utrecht, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cobi J.","family":"Heijnen","sequence":"additional","affiliation":[{"name":"From the Laboratory of Psychoneuroimmunology (C.H.N., C.J.H., A.K.) and the Department of Neonatology (F.G., F.v.B.), University Medical Center Utrecht, Utrecht, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floris","family":"Groenendaal","sequence":"additional","affiliation":[{"name":"From the Laboratory of Psychoneuroimmunology (C.H.N., C.J.H., A.K.) and the Department of Neonatology (F.G., F.v.B.), University Medical Center Utrecht, Utrecht, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"van Bel","sequence":"additional","affiliation":[{"name":"From the Laboratory of Psychoneuroimmunology (C.H.N., C.J.H., A.K.) and the Department of Neonatology (F.G., F.v.B.), University Medical Center Utrecht, Utrecht, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke","family":"Kavelaars","sequence":"additional","affiliation":[{"name":"From the Laboratory of Psychoneuroimmunology (C.H.N., C.J.H., A.K.) and the Department of Neonatology (F.G., F.v.B.), University Medical Center Utrecht, Utrecht, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.07.003"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.wco.0000218229.73678.a8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2003.10.005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207230"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.107.504175"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.108.516401"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2007.09.013"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600342"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210417"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401865"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505671200"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016089607548"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311766200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1124\/mi.2.1.22"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/35104568"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204570"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00301-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.07.003"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(99)00008-8"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-007-9070-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-45"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01610"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-07-j0001.2002"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.109.560250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:33:09Z","timestamp":1715610789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.109.560250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2009,10]]}},"alternative-id":["10.1161\/STROKEAHA.109.560250"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.109.560250","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10]]},"assertion":[{"value":"2009-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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