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
2001 Journal of Neuroscience  
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
more » ... des (ODNs) led to increased infarct volume (45 Ϯ 8%; p Ͻ 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.
doi:10.1523/jneurosci.21-06-01876.2001 pmid:11245672 fatcat:afxt72sovbfcliez66qdbddxa4