{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:16:59Z","timestamp":1791357419268,"version":"4.3.1"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            NF-\u03baB is a transcription factor that regulates inflammatory and apoptotic pathways. We described previously that intraperitoneal administration of the NF-\u03baB inhibitor TAT-NBD at 0 and 3 hours after neonatal hypoxia-ischemia (HI) markedly reduced brain damage. We hypothesize that timing and duration of NF-\u03baB inhibition will be a major factor in determining outcome.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            HI was induced in P7 rats by unilateral carotid artery occlusion and hypoxia. In vivo TAT-NBD effects were determined on cerebral damage, NF-\u03baB activity, cytokine expression, and pro- and antiapoptotic molecules. In vitro effects of TAT-NBD were determined using primary neurons and cell lines.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            HI induced 2 peaks of cerebral NF-\u03baB activity at 3 to 6 and 24 hours after HI. Neuroprotective 0\/3-hour TAT-NBD treatment only inhibited early NF-\u03baB activity. However, inhibition of both early and late NF-\u03baB-activity by 0\/6\/12-hour TAT-NBD or only late NF-\u03baB activity by 18\/21-hour TAT-NBD aggravated damage. 0\/6\/12-hour TAT-NBD did not prevent HI-induced upregulation of cytokines at 24 hours after HI. Protective 0\/3-hour TAT-NBD treatment prevented nuclear accumulation of p53 at 24 hours after HI. Nuclear p53 was not reduced after 0\/6\/12-hour TAT-NBD. Prolonged TAT-NBD increased the proapoptotic factor PUMA and reduced the antiapoptotic factors Bcl-2 and Bcl-xL. Also in neuronal cultures prolonged TAT-NBD exposure overruled protective short-term TAT-NBD treatment.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Early NF-\u03baB activation contributes to neonatal HI brain damage. Late NF-\u03baB provides endogenous neuroprotection and upregulates antiapoptotic molecules. Inhibition of early NF-\u03baB activity is neuroprotective only when late NF-\u03baB activity is maintained. Moreover, cerebral cytokine production can occur independently of NF-\u03baB.\n          <\/jats:p>","DOI":"10.1161\/strokeaha.108.516401","type":"journal-article","created":{"date-parts":[[2008,4,18]],"date-time":"2008-04-18T01:24:42Z","timestamp":1208481882000},"page":"2578-2586","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["A Dual Role of the NF-\u03baB Pathway in Neonatal Hypoxic-Ischemic Brain Damage"],"prefix":"10.1161","volume":"39","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 (C.H.N., F.G., F.v.B.), University Medical Center Utrecht, The Netherlands; and the Department of Animal Biology (M.J.M.), University of Pennsylvania, School of Veterinary Medicine, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 (C.H.N., F.G., F.v.B.), University Medical Center Utrecht, The Netherlands; and the Department of Animal Biology (M.J.M.), University of Pennsylvania, School of Veterinary Medicine, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 (C.H.N., F.G., F.v.B.), University Medical Center Utrecht, The Netherlands; and the Department of Animal Biology (M.J.M.), University of Pennsylvania, School of Veterinary Medicine, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"May","sequence":"additional","affiliation":[{"name":"From the Laboratory of Psychoneuroimmunology (C.H.N., C.J.H., A.K.) and the Department of Neonatology (C.H.N., F.G., F.v.B.), University Medical Center Utrecht, The Netherlands; and the Department of Animal Biology (M.J.M.), University of Pennsylvania, School of Veterinary Medicine, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 (C.H.N., F.G., F.v.B.), University Medical Center Utrecht, The Netherlands; and the Department of Animal Biology (M.J.M.), University of Pennsylvania, School of Veterinary Medicine, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 (C.H.N., F.G., F.v.B.), University Medical Center Utrecht, The Netherlands; and the Department of Animal Biology (M.J.M.), University of Pennsylvania, School of Veterinary Medicine, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.09.005"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2004.17.2.829042"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26274"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2003.10.004"},{"key":"e_1_3_2_6_2","first-page":"28","volume":"35","year":"2002","unstructured":"Shishodia S, Aggarwal BB. Nuclear factor-kappaB activation: a question of life or death. J Biochem Mol Biol. 2002; 35: 28\u201340.","journal-title":"J Biochem Mol Biol"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2003.10.005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207230"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.wco.0000218229.73678.a8"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11916"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","unstructured":"Nijboer CH Heijnen CJ Groenendaal F May MJ van Bel F Kavelaars A (2008) Strong neuroprotection by inhibition of NF-\u03baB after neonatal hypoxia-ischemia involves apoptotic mechanisms but is independent of cytokines. Stroke in press.","DOI":"10.1161\/STROKEAHA.107.504175"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1550"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000196807.10122.5f"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600342"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.02.103"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1323"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0341291"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2005.07.003"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201638"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.03.149"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-14-05910.2002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.06.063"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705462"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600004"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12658-X"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.108.516401","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:16:32Z","timestamp":1715602592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.108.516401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":25,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1161\/STROKEAHA.108.516401"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.108.516401","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9]]},"assertion":[{"value":"2008-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-03-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}