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

Vemuganti L Raghavendra Rao, Aclan Dogan, Kathryn G. Todd, Kellie K. Bowen, Bum Tae Kim, Jeffrey D. Rothstein, Robert J. Dempsey

Research output: Contribution to journalArticle

180 Citations (Scopus)

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. 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 in creased 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.

Original languageEnglish (US)
Pages (from-to)1876-1883
Number of pages8
JournalJournal of Neuroscience
Volume21
Issue number6
StatePublished - Mar 15 2001
Externally publishedYes

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Amino Acid Transport System X-AG
Oligodeoxyribonucleotides
Middle Cerebral Artery Infarction
Transient Ischemic Attack
Neuroglia
Brain
Cerebral Cortex
Glutamic Acid
Stroke
Mortality

Keywords

  • Antisense knockdown
  • EAAC1
  • Focal cerebral ischemia
  • GLT-1
  • Glutamate transporters
  • Middle cerebral artery occlusion
  • Neuronal damage
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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. / Rao, Vemuganti L Raghavendra; Dogan, Aclan; Todd, Kathryn G.; Bowen, Kellie K.; Kim, Bum Tae; Rothstein, Jeffrey D.; Dempsey, Robert J.

In: Journal of Neuroscience, Vol. 21, No. 6, 15.03.2001, p. 1876-1883.

Research output: Contribution to journalArticle

Rao, Vemuganti L Raghavendra ; Dogan, Aclan ; Todd, Kathryn G. ; Bowen, Kellie K. ; Kim, Bum Tae ; Rothstein, Jeffrey D. ; Dempsey, Robert J. / 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. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 6. pp. 1876-1883.
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