Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat
Ischemic/hypoxic brain damage induced in 7-day-old rats was significantly attenuated in a dose-dependent manner by intracerebral injection of glial cell line-derived neurotrophic factor (GDNF; 2 or 4 microg) within 30 min after the insult. Whereas the great majority of the vehicle-treated animals sh...
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| Veröffentlicht in: | Acta neuropathologica 2000-08, Vol.100 (2), p.161-167 |
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| creator | IKEDA, T XIA, X. Y XIA, Y. X IKENOUE, T BORA HAN CHOI, B. H |
| description | Ischemic/hypoxic brain damage induced in 7-day-old rats was significantly attenuated in a dose-dependent manner by intracerebral injection of glial cell line-derived neurotrophic factor (GDNF; 2 or 4 microg) within 30 min after the insult. Whereas the great majority of the vehicle-treated animals showed massive infarction involving more than 75% of the affected cerebral hemisphere, GDNF injection resulted in a remarkable reduction in both the incidence and severity of the brain damage (incidence ranging from 76% to 93% in controls to 34% to 64% in the 2.0-microg group and 7% to 29% in 4.0-microg group). The induction of immunoreactive 70-kDa heat shock protein (HSP70) in cerebral cortical neurons was also significantly reduced in GDNF-treated animals as compared to controls. The mechanisms responsible for the neuroprotective effects of GDNF remain unknown, although it has been speculated that these may be endogeneous. The higher expression of GDNF and its mRNA in developing brains may be one of the factors responsible for the relative resistance to ischemia of fetal and neonatal as opposed to adult brains. GDNF may possibly act by protecting against oxidative stress or by scavenging free radicals generated during ischemia. The results of our study strongly suggest that GDNF may prove to be an effective and potent protective agent against perinatal ischemic/hypoxic encephalopathy. |
| doi_str_mv | 10.1007/s004019900162 |
| format | Article |
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Y ; XIA, Y. X ; IKENOUE, T ; BORA HAN ; CHOI, B. H</creator><creatorcontrib>IKEDA, T ; XIA, X. Y ; XIA, Y. X ; IKENOUE, T ; BORA HAN ; CHOI, B. H</creatorcontrib><description>Ischemic/hypoxic brain damage induced in 7-day-old rats was significantly attenuated in a dose-dependent manner by intracerebral injection of glial cell line-derived neurotrophic factor (GDNF; 2 or 4 microg) within 30 min after the insult. Whereas the great majority of the vehicle-treated animals showed massive infarction involving more than 75% of the affected cerebral hemisphere, GDNF injection resulted in a remarkable reduction in both the incidence and severity of the brain damage (incidence ranging from 76% to 93% in controls to 34% to 64% in the 2.0-microg group and 7% to 29% in 4.0-microg group). The induction of immunoreactive 70-kDa heat shock protein (HSP70) in cerebral cortical neurons was also significantly reduced in GDNF-treated animals as compared to controls. The mechanisms responsible for the neuroprotective effects of GDNF remain unknown, although it has been speculated that these may be endogeneous. The higher expression of GDNF and its mRNA in developing brains may be one of the factors responsible for the relative resistance to ischemia of fetal and neonatal as opposed to adult brains. GDNF may possibly act by protecting against oxidative stress or by scavenging free radicals generated during ischemia. The results of our study strongly suggest that GDNF may prove to be an effective and potent protective agent against perinatal ischemic/hypoxic encephalopathy.</description><identifier>ISSN: 0001-6322</identifier><identifier>EISSN: 1432-0533</identifier><identifier>DOI: 10.1007/s004019900162</identifier><identifier>PMID: 10963363</identifier><identifier>CODEN: ANPTAL</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Animals ; Animals, Newborn - physiology ; Biological and medical sciences ; Brain - drug effects ; Brain - metabolism ; Brain - pathology ; Brain damage ; Brain injury ; Brain Ischemia - drug therapy ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Cerebral Infarction - pathology ; Dose-Response Relationship, Drug ; Encephalopathy ; Fetuses ; Free radicals ; Glial Cell Line-Derived Neurotrophic Factor ; Heat shock proteins ; HSP70 Heat-Shock Proteins - metabolism ; Hsp70 protein ; Hypoxia ; Hypoxia - drug therapy ; Hypoxia - metabolism ; Hypoxia - pathology ; Injection ; Ischemia ; Medical sciences ; mRNA ; Necrosis ; Neonates ; Nerve Growth Factors ; Nerve Tissue Proteins - therapeutic use ; Neurology ; Neuronal-glial interactions ; Neuroprotection ; Neuroprotective Agents - therapeutic use ; Oxidative stress ; Rats ; Rats, Wistar ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Acta neuropathologica, 2000-08, Vol.100 (2), p.161-167</ispartof><rights>2000 INIST-CNRS</rights><rights>Springer-Verlag Berlin Heidelberg 2000.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-f19541ca110a35589a5fb55df88c51fef599c86b4cfaa9672c8fe492d3f4cc4b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1428236$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10963363$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>IKEDA, T</creatorcontrib><creatorcontrib>XIA, X. Y</creatorcontrib><creatorcontrib>XIA, Y. X</creatorcontrib><creatorcontrib>IKENOUE, T</creatorcontrib><creatorcontrib>BORA HAN</creatorcontrib><creatorcontrib>CHOI, B. H</creatorcontrib><title>Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat</title><title>Acta neuropathologica</title><addtitle>Acta Neuropathol</addtitle><description>Ischemic/hypoxic brain damage induced in 7-day-old rats was significantly attenuated in a dose-dependent manner by intracerebral injection of glial cell line-derived neurotrophic factor (GDNF; 2 or 4 microg) within 30 min after the insult. Whereas the great majority of the vehicle-treated animals showed massive infarction involving more than 75% of the affected cerebral hemisphere, GDNF injection resulted in a remarkable reduction in both the incidence and severity of the brain damage (incidence ranging from 76% to 93% in controls to 34% to 64% in the 2.0-microg group and 7% to 29% in 4.0-microg group). The induction of immunoreactive 70-kDa heat shock protein (HSP70) in cerebral cortical neurons was also significantly reduced in GDNF-treated animals as compared to controls. The mechanisms responsible for the neuroprotective effects of GDNF remain unknown, although it has been speculated that these may be endogeneous. The higher expression of GDNF and its mRNA in developing brains may be one of the factors responsible for the relative resistance to ischemia of fetal and neonatal as opposed to adult brains. GDNF may possibly act by protecting against oxidative stress or by scavenging free radicals generated during ischemia. The results of our study strongly suggest that GDNF may prove to be an effective and potent protective agent against perinatal ischemic/hypoxic encephalopathy.</description><subject>Animals</subject><subject>Animals, Newborn - physiology</subject><subject>Biological and medical sciences</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain damage</subject><subject>Brain injury</subject><subject>Brain Ischemia - drug therapy</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Cerebral Infarction - pathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Encephalopathy</subject><subject>Fetuses</subject><subject>Free radicals</subject><subject>Glial Cell Line-Derived Neurotrophic Factor</subject><subject>Heat shock proteins</subject><subject>HSP70 Heat-Shock Proteins - metabolism</subject><subject>Hsp70 protein</subject><subject>Hypoxia</subject><subject>Hypoxia - drug therapy</subject><subject>Hypoxia - metabolism</subject><subject>Hypoxia - pathology</subject><subject>Injection</subject><subject>Ischemia</subject><subject>Medical sciences</subject><subject>mRNA</subject><subject>Necrosis</subject><subject>Neonates</subject><subject>Nerve Growth Factors</subject><subject>Nerve Tissue Proteins - therapeutic use</subject><subject>Neurology</subject><subject>Neuronal-glial interactions</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Oxidative stress</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0001-6322</issn><issn>1432-0533</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpd0U1r3DAQBmBREprttsdegyGhN2f1aVvHsiSbQqCX9GzGY6mrxR8byQ7Zf58pu5A0J6Hh0eiVhrHvgt8IzstV4lxzYS3nopCf2EJoJXNulDpjC07FvFBSXrAvKe1oJ0ttPrMLwW2hVKEWLG66AF2GruuyLgwub10Mz67NBjfHcYrjfhsw84DTGLM9VRxOKYO_EIY0ZSHh1vUBVtvDfnwJkIehnZFON5FAFobdHA-0ULdxgIkuijB9ZeceuuS-ndYl-3N3-7i-zx9-b36tfz7kqIWcci-s0QJBCA7KmMqC8Y0xra8qNMI7b6zFqmg0egBblBIr77SVrfIaUTdqyX4c-1Lsp9mlqe4pLz0UKM2c6lJKYYw2BK8-wN04x4Gy1VITKYXhmlR-VBjHlKLz9T6GHuKhFrz-N4r6v1GQvzx1nZvete_08e8JXJ8AJITORxgwpDenZSXJvQKxBpHK</recordid><startdate>20000801</startdate><enddate>20000801</enddate><creator>IKEDA, T</creator><creator>XIA, X. 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Y ; XIA, Y. X ; IKENOUE, T ; BORA HAN ; CHOI, B. 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Y</au><au>XIA, Y. X</au><au>IKENOUE, T</au><au>BORA HAN</au><au>CHOI, B. H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat</atitle><jtitle>Acta neuropathologica</jtitle><addtitle>Acta Neuropathol</addtitle><date>2000-08-01</date><risdate>2000</risdate><volume>100</volume><issue>2</issue><spage>161</spage><epage>167</epage><pages>161-167</pages><issn>0001-6322</issn><eissn>1432-0533</eissn><coden>ANPTAL</coden><abstract>Ischemic/hypoxic brain damage induced in 7-day-old rats was significantly attenuated in a dose-dependent manner by intracerebral injection of glial cell line-derived neurotrophic factor (GDNF; 2 or 4 microg) within 30 min after the insult. Whereas the great majority of the vehicle-treated animals showed massive infarction involving more than 75% of the affected cerebral hemisphere, GDNF injection resulted in a remarkable reduction in both the incidence and severity of the brain damage (incidence ranging from 76% to 93% in controls to 34% to 64% in the 2.0-microg group and 7% to 29% in 4.0-microg group). The induction of immunoreactive 70-kDa heat shock protein (HSP70) in cerebral cortical neurons was also significantly reduced in GDNF-treated animals as compared to controls. The mechanisms responsible for the neuroprotective effects of GDNF remain unknown, although it has been speculated that these may be endogeneous. The higher expression of GDNF and its mRNA in developing brains may be one of the factors responsible for the relative resistance to ischemia of fetal and neonatal as opposed to adult brains. GDNF may possibly act by protecting against oxidative stress or by scavenging free radicals generated during ischemia. The results of our study strongly suggest that GDNF may prove to be an effective and potent protective agent against perinatal ischemic/hypoxic encephalopathy.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>10963363</pmid><doi>10.1007/s004019900162</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Animals, Newborn - physiology Biological and medical sciences Brain - drug effects Brain - metabolism Brain - pathology Brain damage Brain injury Brain Ischemia - drug therapy Brain Ischemia - metabolism Brain Ischemia - pathology Cerebral Infarction - pathology Dose-Response Relationship, Drug Encephalopathy Fetuses Free radicals Glial Cell Line-Derived Neurotrophic Factor Heat shock proteins HSP70 Heat-Shock Proteins - metabolism Hsp70 protein Hypoxia Hypoxia - drug therapy Hypoxia - metabolism Hypoxia - pathology Injection Ischemia Medical sciences mRNA Necrosis Neonates Nerve Growth Factors Nerve Tissue Proteins - therapeutic use Neurology Neuronal-glial interactions Neuroprotection Neuroprotective Agents - therapeutic use Oxidative stress Rats Rats, Wistar Vascular diseases and vascular malformations of the nervous system |
| title | Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat |
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