COMPARISON OF THE NEUROPROTECTIVE EFFECTS OF APV AND BCL-2 IN GLUTAMATE-INDUCED CELL-DEATH

THE neuroprotective effects of the NMDA receptor blocker APV were comp ared with those of bcl-2 in a glutamate-induced excitotoxic cell death model in cultured rat cortical neurons. Exposure to 100 mu M glutamat e for 5 h caused similar to 95% of the cultured neurons to die in 24 h . The NMDA-selective antagonist D-(-)-2-amino-5-phosphonopentanoate (A PV) protected the neurons effectively when applied prior to or soon af ter glutamate treatment. However, infection with a viral vector expres sing the proto-oncogene bcl-2 strongly protected neurons even if appli ed as late as 8 h following the glutamate insult. These data provides evidence that APV blocks an early stage of the death cascade in respon se to elevations of glutamate. By contrast bcl-2 appears to act at a f airly late stage in the cell death process and these results suggest a possible clinical role in treatment of ischemic brain disorders.