{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:26:19Z","timestamp":1791307579277,"version":"4.3.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            Interactions between excitotoxic, inflammatory, and apoptotic pathways determine outcome in hypoxic-ischemic brain damage. The transcription factor NF-\u03baB has been suggested to enhance brain damage via stimulation of cytokine production. There is also evidence that NF-\u03baB activity is required for neuronal survival. We used the NF-\u03baB inhibitor NBD, coupled to TAT to facilitate cerebral uptake, to determine the neuroprotective capacity of NF-\u03baB inhibition in neonatal hypoxia-ischemia (HI) and to identify its contribution to cerebral inflammation and damage.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            Brain damage was induced in neonatal rats by unilateral carotid artery occlusion and hypoxia and analyzed immunohistochemically; NF-\u03baB activity was analyzed by EMSA. We analyzed cytokine mRNA levels and activation of apoptotic pathways by Western blotting. In vitro effects of TAT-NBD were determined in a neuronal cell line.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Inhibition of cerebral NF-\u03baB activity by TAT-NBD had a significant neuroprotective effect; brain damage was reduced by more than 80% with a therapeutic window of at least 6 hours. In contrast to earlier suggestions, the protective effect of TAT-NBD did not involve suppression of early cytokine upregulation after HI. Moreover, NF-\u03baB inhibition prevented HI-induced upregulation and nuclear as well as mitochondrial accumulation of p53, prevented mitochondrial cytochrome-\n            <jats:italic>c<\/jats:italic>\n            release and activation of caspase-3. Finally, TAT-NBD could directly increase neuronal survival because TAT-NBD was sufficient to inhibit death in a neuronal cell line. A nonactive mutant peptide did not have any effect.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Inhibition of NF-\u03baB has strong neuroprotective effects that involve downregulation of apoptotic molecules but are independent of inhibition of cytokine production.\n          <\/jats:p>","DOI":"10.1161\/strokeaha.107.504175","type":"journal-article","created":{"date-parts":[[2008,4,18]],"date-time":"2008-04-18T01:24:42Z","timestamp":1208481882000},"page":"2129-2137","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["Strong Neuroprotection by Inhibition of NF-\u03baB After Neonatal Hypoxia-Ischemia Involves Apoptotic Mechanisms but Is Independent of Cytokines"],"prefix":"10.1161","volume":"39","author":[{"given":"Cora H.A.","family":"Nijboer","sequence":"first","affiliation":[{"name":"From the Laboratory of Psychoneuroimmunology (C.H.A.N., C.J.H., A.K.) and the Department of Neonatology (C.H.A.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.A.N., C.J.H., A.K.) and the Department of Neonatology (C.H.A.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.A.N., C.J.H., A.K.) and the Department of Neonatology (C.H.A.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.A.N., C.J.H., A.K.) and the Department of Neonatology (C.H.A.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.A.N., C.J.H., A.K.) and the Department of Neonatology (C.H.A.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.A.N., C.J.H., A.K.) and the Department of Neonatology (C.H.A.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":"10.1056\/NEJMra041996"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.09.005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2004.17.2.829042"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02579"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11916"},{"key":"e_1_3_2_7_2","first-page":"28","volume":"35","year":"2002","unstructured":"Shishodia S, Aggarwal BB. 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