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 cer ebral cortex and striatum. Normal functioning of glutamate transporters cle ars the synaptically released glutamate to prevent excitotoxic neuronal dea th. This study evaluated the functional role of the glial (GLT-1) and neuro nal (EAAC1) glutamate transporters in mediating ischemic neuronal damage af ter transient middle cerebral artery occlusion (MCAO). Transient MCAO in ra ts infused with GLT-1 antisense oligodeoxynucleotides (ODNs) led to increas ed infarct volume (45 +/- 8%; p < 0.05), worsened neurological status, and in-creased mortality rate, compared with GLT-1 sense/random ODN-infused con trols. Transient MCAO in rats infused with EAAC1 antisense ODNs had no sign ificant effect on any of these parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurologic al deficit after stroke.