{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:09:00Z","timestamp":1785499740531,"version":"3.56.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p> We have shown earlier that 2-iminobiotin (2-IB) reduces hypoxia-ischemia (HI)-induced brain damage in neonatal rats, and presumed that inhibition of nitric oxide synthases (NOS) was the underlying mechanism. We now investigated the effect of 2-IB treatment in P7 rat pups to determine the role of gender and the neuroprotective mechanism. Pups were subjected to HI (occlusion of right carotid artery and 120 mins FiO<jats:sub>2<\/jats:sub> 0.08) and received subcutaneous (s.c.) 10 mg\/kg 2-IB at 0, 12 and 24 h after hypoxia. After 6 weeks, neuronal damage was assessed histologically. We determined cerebral nitrite and nitrate (NO<jats:sub>x<\/jats:sub>) and nitrotyrosine, heat-shock protein 70, cytosolic cytochrome c, cleaved caspase 3, nuclear translocation of apoptosis-inducing factor (AIF) and the effect of 2-IB on NOS activity in cultured cells. 2-Iminobiotin treatment reduced long-term brain damage in female but not male rats. Unexpectedly, 2-IB treatment did not reduce cerebral NO<jats:sub>x<\/jats:sub> or nitrotyrosine levels, and did not inhibit NOS activity in vitro. The gender-dependent neuroprotective effect of 2-IB was reflected in inhibition of the HI-induced increase in cytosolic cytochrome c and cleaved caspase 3 in females only. Hypoxia\u2013ischemia-induced activation of AIF was observed in males only and was not affected by 2-IB. Post-HI treatment with 2-IB provides gender-specific long- and short-term neuroprotection in female P7 rats via inhibition of the cytochrome c-caspase 3 neuronal death pathway. 2-Iminobiotin did not alter cerebral NO<jats:sub>x<\/jats:sub> nor inhibited NOS in intact cells. Therefore, we conclude that it is highly unlikely that the neuroprotective effect of 2-IB involves NOS inhibition. <\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600342","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T16:01:16Z","timestamp":1149091276000},"page":"282-292","source":"Crossref","is-referenced-by-count":108,"title":["Gender-Specific Neuroprotection by 2-Iminobiotin after Hypoxia\u2014Ischemia in the Neonatal Rat via a Nitric Oxide Independent Pathway"],"prefix":"10.1177","volume":"27","author":[{"given":"Cora HA","family":"Nijboer","sequence":"first","affiliation":[{"name":"Laboratory for Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands"},{"name":"Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris","family":"Groenendaal","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Kavelaars","sequence":"additional","affiliation":[{"name":"Laboratory for Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik H","family":"Hagberg","sequence":"additional","affiliation":[{"name":"Perinatal Center, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"van Bel","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cobi J","family":"Heijnen","sequence":"additional","affiliation":[{"name":"Laboratory for Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2007,2,1]]},"reference":[{"key":"bibr1-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.1.159"},{"key":"bibr2-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2005.03.002"},{"key":"bibr3-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1038\/nn1624"},{"key":"bibr4-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-200204000-00005"},{"key":"bibr5-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405461200"},{"key":"bibr6-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041996"},{"key":"bibr7-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)90385-9"},{"key":"bibr8-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1159\/000069040"},{"key":"bibr9-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02547.x"},{"key":"bibr10-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000054051.88378.25"},{"key":"bibr11-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000153064.41332.f6"},{"key":"bibr12-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1007\/s004410000199"},{"key":"bibr13-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90094-5"},{"key":"bibr14-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(03)00076-6"},{"key":"bibr15-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600059"},{"key":"bibr16-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1993.1449"},{"key":"bibr17-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2005.07.003"},{"key":"bibr18-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600194"},{"key":"bibr19-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000028343.25901.09"},{"key":"bibr20-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410090206"},{"key":"bibr21-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/0378-3782(91)90044-4"},{"key":"bibr22-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207523"},{"key":"bibr23-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2554"},{"key":"bibr24-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.8.1666"},{"key":"bibr25-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1159\/000069044"},{"key":"bibr26-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600007"},{"key":"bibr27-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000200799.64038.19"},{"key":"bibr28-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.06.031"},{"key":"bibr29-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012532104-4\/50071-8"},{"key":"bibr30-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3461-04.2004"},{"key":"bibr31-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(96)00006-1"},{"key":"bibr32-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072221"},{"key":"bibr33-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02500.x"},{"key":"bibr34-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401545"},{"key":"bibr35-sj.jcbfm.9600342","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03639.x"}],"container-title":["Journal 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