Sustained hypoxia-ischemia results in reactive nitrogen and oxygen species production and injury in the premature fetal rabbit brain
Free radical-mediated injury is implicated in hypoxic-ischemic encephalopathy observed in neonates. We investigated in utero free radical production and injury following hypoxia-ischemia to premature fetal brain utilizing a rabbit model of acute placental insufficiency. Pregnant rabbits at 29 days g...
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| Veröffentlicht in: | Journal of neuropathology and experimental neurology 1998-06, Vol.57 (6), p.544-553 |
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| container_title | Journal of neuropathology and experimental neurology |
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| creator | SIDHARTHA TAN FEN ZHOU NIELSEN, V. G ZIWEI WANG GLADSON, C. L PARKS, D. A |
| description | Free radical-mediated injury is implicated in hypoxic-ischemic encephalopathy observed in neonates. We investigated in utero free radical production and injury following hypoxia-ischemia to premature fetal brain utilizing a rabbit model of acute placental insufficiency. Pregnant rabbits at 29 days gestation were randomized to uterine ischemia for 50 minutes (min) (hypoxia) or nonischemic controls. Fetal brains were obtained immediately after ischemia for oxidative and acute-injury markers or 24 hours (h) post-ischemia for histopathology. Nitrotyrosine formation, a marker of NO-derived species such as peroxynitrite, was observed only in hypoxic brains. Hypoxia resulted in a significant increase in nitrogen oxides, lipid peroxidation, and protein oxidation, with a concomitant decrease in total antioxidant capacity, compared with controls. Peroxynitrite addition to brain homogenate increased nitrogen oxides linearly (1:1), although protein carbonyls were unchanged. Concomitantly, in vitro cortical and hippocampal cell viability and ATP levels decreased, with an increase in brain edema in hypoxic brains. Fetuses delivered 24 h post-ischemia had increased hippocampal nuclear karyorrhexis on histology compared with controls. Antioxidant administration (ascorbic acid and Trolox) intraperitoneally ameliorated changes in cellular viability and brain edema. Acute fetal hypoxia-ischemia without reoxygenation results in increased nitrogen and oxygen free radical production that may cause brain injury. The merits of the described model are discussed. |
| doi_str_mv | 10.1097/00005072-199806000-00002 |
| format | Article |
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Hypoxia resulted in a significant increase in nitrogen oxides, lipid peroxidation, and protein oxidation, with a concomitant decrease in total antioxidant capacity, compared with controls. Peroxynitrite addition to brain homogenate increased nitrogen oxides linearly (1:1), although protein carbonyls were unchanged. Concomitantly, in vitro cortical and hippocampal cell viability and ATP levels decreased, with an increase in brain edema in hypoxic brains. Fetuses delivered 24 h post-ischemia had increased hippocampal nuclear karyorrhexis on histology compared with controls. Antioxidant administration (ascorbic acid and Trolox) intraperitoneally ameliorated changes in cellular viability and brain edema. Acute fetal hypoxia-ischemia without reoxygenation results in increased nitrogen and oxygen free radical production that may cause brain injury. The merits of the described model are discussed.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1097/00005072-199806000-00002</identifier><identifier>PMID: 9630234</identifier><identifier>CODEN: JNENAD</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Analysis ; Animals ; Antioxidants (Nutrients) ; Antioxidants - pharmacology ; Ascorbic Acid - pharmacology ; Biological and medical sciences ; Brain ; Brain - cytology ; Brain - embryology ; Brain - metabolism ; Brain Ischemia - metabolism ; Cell Death - drug effects ; Cell Survival - drug effects ; Chromans - pharmacology ; Female ; Free Radicals - metabolism ; Hypoxia, Brain - metabolism ; Ischemia ; Lipid peroxidation ; Medical sciences ; Neurology ; Nitrogen - metabolism ; Nitrogen oxides ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; Pregnancy ; Pregnant women ; Rabbits ; Reactive Oxygen Species - metabolism ; Uterus - blood supply ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Journal of neuropathology and experimental neurology, 1998-06, Vol.57 (6), p.544-553</ispartof><rights>1998 INIST-CNRS</rights><rights>COPYRIGHT 1998 Oxford University Press</rights><rights>Copyright American Association of Neuropathologists, Inc. 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A</creatorcontrib><title>Sustained hypoxia-ischemia results in reactive nitrogen and oxygen species production and injury in the premature fetal rabbit brain</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>Free radical-mediated injury is implicated in hypoxic-ischemic encephalopathy observed in neonates. We investigated in utero free radical production and injury following hypoxia-ischemia to premature fetal brain utilizing a rabbit model of acute placental insufficiency. Pregnant rabbits at 29 days gestation were randomized to uterine ischemia for 50 minutes (min) (hypoxia) or nonischemic controls. Fetal brains were obtained immediately after ischemia for oxidative and acute-injury markers or 24 hours (h) post-ischemia for histopathology. Nitrotyrosine formation, a marker of NO-derived species such as peroxynitrite, was observed only in hypoxic brains. Hypoxia resulted in a significant increase in nitrogen oxides, lipid peroxidation, and protein oxidation, with a concomitant decrease in total antioxidant capacity, compared with controls. Peroxynitrite addition to brain homogenate increased nitrogen oxides linearly (1:1), although protein carbonyls were unchanged. Concomitantly, in vitro cortical and hippocampal cell viability and ATP levels decreased, with an increase in brain edema in hypoxic brains. Fetuses delivered 24 h post-ischemia had increased hippocampal nuclear karyorrhexis on histology compared with controls. Antioxidant administration (ascorbic acid and Trolox) intraperitoneally ameliorated changes in cellular viability and brain edema. Acute fetal hypoxia-ischemia without reoxygenation results in increased nitrogen and oxygen free radical production that may cause brain injury. The merits of the described model are discussed.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antioxidants (Nutrients)</subject><subject>Antioxidants - pharmacology</subject><subject>Ascorbic Acid - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Brain - cytology</subject><subject>Brain - embryology</subject><subject>Brain - metabolism</subject><subject>Brain Ischemia - metabolism</subject><subject>Cell Death - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chromans - pharmacology</subject><subject>Female</subject><subject>Free Radicals - metabolism</subject><subject>Hypoxia, Brain - metabolism</subject><subject>Ischemia</subject><subject>Lipid peroxidation</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Nitrogen - metabolism</subject><subject>Nitrogen oxides</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Pregnancy</subject><subject>Pregnant women</subject><subject>Rabbits</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Uterus - blood supply</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdUU2P0zAQtRBoKQs_AclCiFsW24nt-Lha8SWtxAE4RxNnsnWVOsV20PbOD2dCSw_YB8-8ec_zxRiX4kYKZ98LOlpYVUnnWmHIq1ZIPWEbqXVTGW3bp2xDiKpqYdxz9iLnHTGccM0Vu3KmFqpuNuz3tyUXCBEHvj0e5scAVch-i_sAPGFeppJ5iGSCL-EX8hhKmh8wcogDnx-Pq5kP6ANmfkjzsBBtPkVD3C3puKrLFimIeyhLQj5igYkn6PtQeJ8o-Uv2bIQp46vze81-fPzw_e5zdf_105e72_vKN1qXyoJ3rpFATm9HIRpvtFHKkYVaKW_FYGsYXO9tTVMB65u-HdeOe-W0EPU1e3f6lyr9uWAu3Z6axWmCiPOSO-tcbZ0xRHzzH3E3LylSbR3lM63UUhPp5kR6gAm7EMe5JPB0B5qenyOOgfBbXRtprdKSBO1J4NOcc8KxO6Swh3TspOjWtXb_1tpd1voXUiR9fS5o6fc4XITnPVL87TkO2cM0Jog-5AtNKaOEbus_kk6qnw</recordid><startdate>19980601</startdate><enddate>19980601</enddate><creator>SIDHARTHA TAN</creator><creator>FEN ZHOU</creator><creator>NIELSEN, V. 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G</au><au>ZIWEI WANG</au><au>GLADSON, C. L</au><au>PARKS, D. A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sustained hypoxia-ischemia results in reactive nitrogen and oxygen species production and injury in the premature fetal rabbit brain</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>1998-06-01</date><risdate>1998</risdate><volume>57</volume><issue>6</issue><spage>544</spage><epage>553</epage><pages>544-553</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><coden>JNENAD</coden><abstract>Free radical-mediated injury is implicated in hypoxic-ischemic encephalopathy observed in neonates. We investigated in utero free radical production and injury following hypoxia-ischemia to premature fetal brain utilizing a rabbit model of acute placental insufficiency. Pregnant rabbits at 29 days gestation were randomized to uterine ischemia for 50 minutes (min) (hypoxia) or nonischemic controls. Fetal brains were obtained immediately after ischemia for oxidative and acute-injury markers or 24 hours (h) post-ischemia for histopathology. Nitrotyrosine formation, a marker of NO-derived species such as peroxynitrite, was observed only in hypoxic brains. Hypoxia resulted in a significant increase in nitrogen oxides, lipid peroxidation, and protein oxidation, with a concomitant decrease in total antioxidant capacity, compared with controls. Peroxynitrite addition to brain homogenate increased nitrogen oxides linearly (1:1), although protein carbonyls were unchanged. Concomitantly, in vitro cortical and hippocampal cell viability and ATP levels decreased, with an increase in brain edema in hypoxic brains. Fetuses delivered 24 h post-ischemia had increased hippocampal nuclear karyorrhexis on histology compared with controls. Antioxidant administration (ascorbic acid and Trolox) intraperitoneally ameliorated changes in cellular viability and brain edema. Acute fetal hypoxia-ischemia without reoxygenation results in increased nitrogen and oxygen free radical production that may cause brain injury. The merits of the described model are discussed.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>9630234</pmid><doi>10.1097/00005072-199806000-00002</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0022-3069 |
| ispartof | Journal of neuropathology and experimental neurology, 1998-06, Vol.57 (6), p.544-553 |
| issn | 0022-3069 1554-6578 |
| language | eng |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Analysis Animals Antioxidants (Nutrients) Antioxidants - pharmacology Ascorbic Acid - pharmacology Biological and medical sciences Brain Brain - cytology Brain - embryology Brain - metabolism Brain Ischemia - metabolism Cell Death - drug effects Cell Survival - drug effects Chromans - pharmacology Female Free Radicals - metabolism Hypoxia, Brain - metabolism Ischemia Lipid peroxidation Medical sciences Neurology Nitrogen - metabolism Nitrogen oxides Oxidative Stress - drug effects Oxidative Stress - physiology Pregnancy Pregnant women Rabbits Reactive Oxygen Species - metabolism Uterus - blood supply Vascular diseases and vascular malformations of the nervous system |
| title | Sustained hypoxia-ischemia results in reactive nitrogen and oxygen species production and injury in the premature fetal rabbit brain |
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