Attenuation of Focal Cerebral Ischemic Injury in Transgenic Mice Overexpressing CuZn Superoxide Dismutase
Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1991-12, Vol.88 (24), p.11158-11162 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | KINOUCHI, H EPSTEIN, C. J MIZUI, T CARLSON, E CHEN, S. F CHAN, P. H |
| description | Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia. |
| doi_str_mv | 10.1073/pnas.88.24.11158 |
| format | Article |
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J ; MIZUI, T ; CARLSON, E ; CHEN, S. F ; CHAN, P. H</creator><creatorcontrib>KINOUCHI, H ; EPSTEIN, C. J ; MIZUI, T ; CARLSON, E ; CHEN, S. F ; CHAN, P. H</creatorcontrib><description>Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.88.24.11158</identifier><identifier>PMID: 1763030</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Animals ; ascorbic acid ; Ascorbic Acid - analysis ; Biological and medical sciences ; Body Water - physiology ; Brain - physiopathology ; Brain Chemistry ; Brain edema ; Brain ischemia ; Cell physiology ; Cerebral cortex ; Cerebral Cortex - chemistry ; Cerebral Cortex - pathology ; Cerebral hemispheres ; Cerebral Infarction - pathology ; Cerebral Infarction - physiopathology ; Free radicals ; Fundamental and applied biological sciences. Psychology ; glutathione ; Glutathione - analysis ; Humans ; Ischemia ; Ischemic Attack, Transient - genetics ; Ischemic Attack, Transient - physiopathology ; Male ; Mice ; Mice, Transgenic ; Moisture content ; Molecular and cellular biology ; superoxide dismutase ; Superoxide Dismutase - genetics ; Superoxide Dismutase - physiology ; Superoxides ; Transgenic animals ; transgenic mice</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1991-12, Vol.88 (24), p.11158-11162</ispartof><rights>Copyright 1991 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-c507bc89ee771f3bbe6289c177f6dd7c09526c77abc4ab6bab3ba4d733b584ff3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/88/24.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2359203$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2359203$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5225964$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1763030$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KINOUCHI, H</creatorcontrib><creatorcontrib>EPSTEIN, C. J</creatorcontrib><creatorcontrib>MIZUI, T</creatorcontrib><creatorcontrib>CARLSON, E</creatorcontrib><creatorcontrib>CHEN, S. F</creatorcontrib><creatorcontrib>CHAN, P. H</creatorcontrib><title>Attenuation of Focal Cerebral Ischemic Injury in Transgenic Mice Overexpressing CuZn Superoxide Dismutase</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.</description><subject>Animals</subject><subject>ascorbic acid</subject><subject>Ascorbic Acid - analysis</subject><subject>Biological and medical sciences</subject><subject>Body Water - physiology</subject><subject>Brain - physiopathology</subject><subject>Brain Chemistry</subject><subject>Brain edema</subject><subject>Brain ischemia</subject><subject>Cell physiology</subject><subject>Cerebral cortex</subject><subject>Cerebral Cortex - chemistry</subject><subject>Cerebral Cortex - pathology</subject><subject>Cerebral hemispheres</subject><subject>Cerebral Infarction - pathology</subject><subject>Cerebral Infarction - physiopathology</subject><subject>Free radicals</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>glutathione</subject><subject>Glutathione - analysis</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Ischemic Attack, Transient - genetics</subject><subject>Ischemic Attack, Transient - physiopathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Moisture content</subject><subject>Molecular and cellular biology</subject><subject>superoxide dismutase</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - physiology</subject><subject>Superoxides</subject><subject>Transgenic animals</subject><subject>transgenic mice</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v0zAYxiMEGmVw5wDCB4S4tPgrsSNxmToGlYZ2YFy4WLbzpnOVOMF2pu6_n0tLYRe42Jaf3_N-6CmKlwQvCBbsw-h1XEi5oHxBCCnlo2JGcE3mFa_x42KGMRVzySl_WjyLcYMxrkuJT4oTIiqGGZ4V7iwl8JNObvBoaNHFYHWHlhDAhPxYRXsDvbNo5TdTuEPOo-ugfVyDz59fnQV0dZvh7RggRufXaDn98OjbNEIYtq4BdO5iPyUd4XnxpNVdhBeH-7T4fvHpevllfnn1ebU8u5zbsmYpn1gYK2sAIUjLjIGKytoSIdqqaYTNG9DKCqGN5dpURhtmNG8EY6aUvG3ZafFxX3ecTA-NBZ_yJmoMrtfhTg3aqYeKdzdqPdyqkuGaZfu7gz0MPyeISfUuWug67WGYohK0rDEn8r8gqbDkkvAM4j1owxBjgPY4C8Fql6LapaikVJSrXylmy-u_d_hj2MeW9bcHXcecV5sjsS4esZLmIatd5zcHbNfgt_qw0ft_E6qdui7BNmX01R7dxDSEI0tZWVPM2D0mpcpr</recordid><startdate>19911215</startdate><enddate>19911215</enddate><creator>KINOUCHI, H</creator><creator>EPSTEIN, C. 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H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-c507bc89ee771f3bbe6289c177f6dd7c09526c77abc4ab6bab3ba4d733b584ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animals</topic><topic>ascorbic acid</topic><topic>Ascorbic Acid - analysis</topic><topic>Biological and medical sciences</topic><topic>Body Water - physiology</topic><topic>Brain - physiopathology</topic><topic>Brain Chemistry</topic><topic>Brain edema</topic><topic>Brain ischemia</topic><topic>Cell physiology</topic><topic>Cerebral cortex</topic><topic>Cerebral Cortex - chemistry</topic><topic>Cerebral Cortex - pathology</topic><topic>Cerebral hemispheres</topic><topic>Cerebral Infarction - pathology</topic><topic>Cerebral Infarction - physiopathology</topic><topic>Free radicals</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>glutathione</topic><topic>Glutathione - analysis</topic><topic>Humans</topic><topic>Ischemia</topic><topic>Ischemic Attack, Transient - genetics</topic><topic>Ischemic Attack, Transient - physiopathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Moisture content</topic><topic>Molecular and cellular biology</topic><topic>superoxide dismutase</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - physiology</topic><topic>Superoxides</topic><topic>Transgenic animals</topic><topic>transgenic mice</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KINOUCHI, H</creatorcontrib><creatorcontrib>EPSTEIN, C. J</creatorcontrib><creatorcontrib>MIZUI, T</creatorcontrib><creatorcontrib>CARLSON, E</creatorcontrib><creatorcontrib>CHEN, S. F</creatorcontrib><creatorcontrib>CHAN, P. 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J</au><au>MIZUI, T</au><au>CARLSON, E</au><au>CHEN, S. F</au><au>CHAN, P. H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Attenuation of Focal Cerebral Ischemic Injury in Transgenic Mice Overexpressing CuZn Superoxide Dismutase</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1991-12-15</date><risdate>1991</risdate><volume>88</volume><issue>24</issue><spage>11158</spage><epage>11162</epage><pages>11158-11162</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1763030</pmid><doi>10.1073/pnas.88.24.11158</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1991-12, Vol.88 (24), p.11158-11162 |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals ascorbic acid Ascorbic Acid - analysis Biological and medical sciences Body Water - physiology Brain - physiopathology Brain Chemistry Brain edema Brain ischemia Cell physiology Cerebral cortex Cerebral Cortex - chemistry Cerebral Cortex - pathology Cerebral hemispheres Cerebral Infarction - pathology Cerebral Infarction - physiopathology Free radicals Fundamental and applied biological sciences. Psychology glutathione Glutathione - analysis Humans Ischemia Ischemic Attack, Transient - genetics Ischemic Attack, Transient - physiopathology Male Mice Mice, Transgenic Moisture content Molecular and cellular biology superoxide dismutase Superoxide Dismutase - genetics Superoxide Dismutase - physiology Superoxides Transgenic animals transgenic mice |
| title | Attenuation of Focal Cerebral Ischemic Injury in Transgenic Mice Overexpressing CuZn Superoxide Dismutase |
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