Antisense Knockdown of the Glial Glutamate Transporter GLT-1, But Not the Neuronal Glutamate Transporter EAAC1, Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain
Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. This study evaluated the functional role of the glial (GLT-1) and neuro...
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| Veröffentlicht in: | The Journal of neuroscience 2001-03, Vol.21 (6), p.1876-1883 |
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| container_title | The Journal of neuroscience |
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| creator | Rao, Vemuganti L. Raghavendra Dogan, Aclan Todd, Kathryn G Bowen, Kellie K Kim, Bum-Tae Rothstein, Jeffrey D Dempsey, Robert J |
| description | Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. This study evaluated the functional role of the glial (GLT-1) and neuronal (EAAC1) glutamate transporters in mediating ischemic neuronal damage after transient middle cerebral artery occlusion (MCAO). Transient MCAO in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) led to increased infarct volume (45 +/- 8%; p < 0.05), worsened neurological status, and increased mortality rate, compared with GLT-1 sense/random ODN-infused controls. Transient MCAO in rats infused with EAAC1 antisense ODNs had no significant effect on any of these parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurological deficit after stroke. |
| doi_str_mv | 10.1523/jneurosci.21-06-01876.2001 |
| format | Article |
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Raghavendra ; Dogan, Aclan ; Todd, Kathryn G ; Bowen, Kellie K ; Kim, Bum-Tae ; Rothstein, Jeffrey D ; Dempsey, Robert J</creator><creatorcontrib>Rao, Vemuganti L. Raghavendra ; Dogan, Aclan ; Todd, Kathryn G ; Bowen, Kellie K ; Kim, Bum-Tae ; Rothstein, Jeffrey D ; Dempsey, Robert J</creatorcontrib><description>Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. This study evaluated the functional role of the glial (GLT-1) and neuronal (EAAC1) glutamate transporters in mediating ischemic neuronal damage after transient middle cerebral artery occlusion (MCAO). Transient MCAO in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) led to increased infarct volume (45 +/- 8%; p < 0.05), worsened neurological status, and increased mortality rate, compared with GLT-1 sense/random ODN-infused controls. Transient MCAO in rats infused with EAAC1 antisense ODNs had no significant effect on any of these parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurological deficit after stroke.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/jneurosci.21-06-01876.2001</identifier><identifier>PMID: 11245672</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Amino Acid Transport System X-AG ; Animals ; ATP-Binding Cassette Transporters - antagonists & inhibitors ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Blood Flow Velocity - drug effects ; Brain - metabolism ; Brain - pathology ; Carrier Proteins - antagonists & inhibitors ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cerebral Cortex - blood supply ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; Cerebrovascular Circulation - drug effects ; Corpus Striatum - blood supply ; Corpus Striatum - metabolism ; Corpus Striatum - pathology ; Disease Progression ; Excitatory Amino Acid Transporter 3 ; Glutamate Plasma Membrane Transport Proteins ; Glutamic Acid - metabolism ; Infarction, Middle Cerebral Artery ; Ischemic Attack, Transient - metabolism ; Ischemic Attack, Transient - pathology ; Male ; Neuroglia - metabolism ; Neuroglia - pathology ; Neurons - metabolism ; Neurons - pathology ; Oligonucleotides, Antisense - pharmacology ; Rats ; Rats, Inbred SHR ; Survival Rate ; Symporters</subject><ispartof>The Journal of neuroscience, 2001-03, Vol.21 (6), p.1876-1883</ispartof><rights>Copyright © 2001 Society for Neuroscience 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-830c6e8abdf8f91c42d1cb5fb0f43fb09038102777d9bfea9002b4da9e58e8103</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762628/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762628/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11245672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rao, Vemuganti L. Raghavendra</creatorcontrib><creatorcontrib>Dogan, Aclan</creatorcontrib><creatorcontrib>Todd, Kathryn G</creatorcontrib><creatorcontrib>Bowen, Kellie K</creatorcontrib><creatorcontrib>Kim, Bum-Tae</creatorcontrib><creatorcontrib>Rothstein, Jeffrey D</creatorcontrib><creatorcontrib>Dempsey, Robert J</creatorcontrib><title>Antisense Knockdown of the Glial Glutamate Transporter GLT-1, But Not the Neuronal Glutamate Transporter EAAC1, Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. 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This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurological deficit after stroke.</description><subject>Amino Acid Transport System X-AG</subject><subject>Animals</subject><subject>ATP-Binding Cassette Transporters - antagonists & inhibitors</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Blood Flow Velocity - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Carrier Proteins - antagonists & inhibitors</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cerebral Cortex - blood supply</subject><subject>Cerebral Cortex - metabolism</subject><subject>Cerebral Cortex - pathology</subject><subject>Cerebrovascular Circulation - drug effects</subject><subject>Corpus Striatum - blood supply</subject><subject>Corpus Striatum - metabolism</subject><subject>Corpus Striatum - pathology</subject><subject>Disease Progression</subject><subject>Excitatory Amino Acid Transporter 3</subject><subject>Glutamate Plasma Membrane Transport Proteins</subject><subject>Glutamic Acid - metabolism</subject><subject>Infarction, Middle Cerebral Artery</subject><subject>Ischemic Attack, Transient - metabolism</subject><subject>Ischemic Attack, Transient - pathology</subject><subject>Male</subject><subject>Neuroglia - metabolism</subject><subject>Neuroglia - pathology</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Survival Rate</subject><subject>Symporters</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFktFu0zAYhSMEYmXwCsjigitSbCdxEi6QutKVQtVJo7u2HOdP65HYne2Q7fV4Mty1onCBuLEt_ed8OrZPFL0heEwymry_1dBb46QaUxJjFmNS5GxMMSZPolFQlDFNMXkajTDNcczSPD2LXjh3izHOMcmfR2eE0DRjOR1FPyfaKwfaAfqqjfxem0Ej0yC_BTRvlWjD2nvRCQ9obYV2O2M9WDRfrmPyDl30Hq2Mf5Sv9qn0Px2zyWQaHLN7IcFWYeoOYwXao0sjg3EKFiobDgsnt9ApES903UuoT-xPAbwBpDS6Fh5dWKH0y-hZI1oHr477eXRzOVtPP8fLq_liOlnGMi1SHxcJlgwKUdVN0ZREprQmssqaCjdpEtYSJwUJL5bndVk1IEqMaZXWooSsgDBJzqOPB-6urzqoZcgdsvKdVZ2wD9wIxf-eaLXlG_ODs5xRRosAeHsEWHPXg_O8U05C2woNpnc8Z2X4k7T8r5AUpMjKck_8cBDK0AdnofmdhmC-7wr_sprdXF99my44JRwz_tgVvu9KML_-8z4n67EcpxhbtdkOygJ3nWjbICd8GIYAZHyPS34BpjbN7g</recordid><startdate>20010315</startdate><enddate>20010315</enddate><creator>Rao, Vemuganti L. 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Raghavendra</au><au>Dogan, Aclan</au><au>Todd, Kathryn G</au><au>Bowen, Kellie K</au><au>Kim, Bum-Tae</au><au>Rothstein, Jeffrey D</au><au>Dempsey, Robert J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antisense Knockdown of the Glial Glutamate Transporter GLT-1, But Not the Neuronal Glutamate Transporter EAAC1, Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2001-03-15</date><risdate>2001</risdate><volume>21</volume><issue>6</issue><spage>1876</spage><epage>1883</epage><pages>1876-1883</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. 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| issn | 0270-6474 1529-2401 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Amino Acid Transport System X-AG Animals ATP-Binding Cassette Transporters - antagonists & inhibitors ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism Blood Flow Velocity - drug effects Brain - metabolism Brain - pathology Carrier Proteins - antagonists & inhibitors Carrier Proteins - genetics Carrier Proteins - metabolism Cerebral Cortex - blood supply Cerebral Cortex - metabolism Cerebral Cortex - pathology Cerebrovascular Circulation - drug effects Corpus Striatum - blood supply Corpus Striatum - metabolism Corpus Striatum - pathology Disease Progression Excitatory Amino Acid Transporter 3 Glutamate Plasma Membrane Transport Proteins Glutamic Acid - metabolism Infarction, Middle Cerebral Artery Ischemic Attack, Transient - metabolism Ischemic Attack, Transient - pathology Male Neuroglia - metabolism Neuroglia - pathology Neurons - metabolism Neurons - pathology Oligonucleotides, Antisense - pharmacology Rats Rats, Inbred SHR Survival Rate Symporters |
| title | Antisense Knockdown of the Glial Glutamate Transporter GLT-1, But Not the Neuronal Glutamate Transporter EAAC1, Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain |
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