Glutamate neurotoxicity has been implicated in stroke, head trauma, multipl
e sclerosis and neurodegenerative diseases. Although recent data show that
cultured glioma cells secrete glutamate, the growth potential of brain tumo
rs has not yet been linked to an excitotoxic mechanism. Using bioluminescen
ce detection of glutamate release from freshly prepared brain slices, we sh
ow that implanted glioma cells continue to secrete glutamate. Moreover, gli
omas with high glutamate release have a distinct growth advantage in host b
rain that is not present in vitro. Treatment with the NMDA receptor antagon
ists MK801 or memantine slowed the growth of glutamate-secreting tumors in
situ, suggesting that activation of NMDA receptors facilitates tumor expans
ion. These findings support a new approach for therapy of brain tumors, bas
ed upon antagonizing glutamate secretion or its target receptors.