{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:24:21Z","timestamp":1767893061517,"version":"3.49.0"},"reference-count":43,"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":[[2002,9]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            Perinatal hypoxia-ischemia is a major cause of neonatal morbidity and mortality. Until now no established neuroprotective intervention after perinatal hypoxia-ischemia has been available. The delay in cell death after perinatal hypoxia-ischemia creates possibilities for therapeutic intervention after the initial insult. Excessive nitric oxide and reactive oxygen species generated on hypoxia-ischemia and reperfusion play a key role in the neurotoxic cascade. The present study examines the neuroprotective properties of neuronal and inducible but not endothelial nitric oxide synthase inhibition by 2-iminobiotin in a piglet model of perinatal hypoxia-ischemia.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            Twenty-three newborn piglets were subjected to 60 minutes of hypoxia-ischemia, followed by 24 hours of reperfusion and reoxygenation. Five additional piglets served as sham-operated controls. On reperfusion, piglets were randomly treated with either vehicle (n=12) or 2-iminobiotin (n=11). At 24 hours after hypoxia-ischemia, the cerebral energy state, presence of vasogenic edema, amount of apparently normal neuronal cells, caspase-3 activity, amount of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL)-positive cells, and degree of tyrosine nitration were assessed.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            A 90% improvement in cerebral energy state, 90% reduction in vasogenic edema, and 60% to 80% reduction in apoptosis-related neuronal cell death were demonstrated in 2-iminobiotin-treated piglets at 24 hours after hypoxia- ischemia. A significant reduction in tyrosine nitration in the cerebral cortex was observed in 2-iminobiotin-treated piglets, indicating decreased formation of reactive nitrogen species.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Simultaneous and selective inhibition of neuronal and inducible nitric oxide synthase by 2-iminobiotin is a promising strategy for neuroprotection after perinatal hypoxia-ischemia.\n          <\/jats:p>","DOI":"10.1161\/01.str.0000028343.25901.09","type":"journal-article","created":{"date-parts":[[2002,9,5]],"date-time":"2002-09-05T21:22:30Z","timestamp":1031260950000},"page":"2304-2310","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Neuroprotection by Selective Nitric Oxide Synthase Inhibition at 24 Hours After Perinatal Hypoxia-Ischemia"],"prefix":"10.1161","volume":"33","author":[{"given":"Cacha","family":"Peeters-Scholte","sequence":"first","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Koster","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wouter","family":"Veldhuis","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"van den Tweel","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changlian","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Kops","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klas","family":"Blomgren","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dop","family":"Ba\u0308r","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"van Buul-Offers","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik","family":"Hagberg","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaas","family":"Nicolay","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"van Bel","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); Department of Experimental In Vivo Nuclear Magnetic Resonance, Image Sciences Institute (W.V., K.N.); Departments of Experimental Neurology (D.B.) and Pediatric Endocrinology (N.K., S. van B-O.), University Medical Center Utrecht, Utrecht, Netherlands; and Perinatal Center, Institute of Physiology and Pharmacology, Go\u0308teborg University, Go\u0308teborg, Sweden (C.Z., K.B., H.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floris","family":"Groenendaal","sequence":"additional","affiliation":[{"name":"From the Department of Neonatology, Wilhelmina Children\u2019s Hospital (C.P-S., J.K., E. van den T., F. van B., F.G.); 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