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 compared with those of bcl-2 in a glutamate-induced excitotoxic cell death model in cultured rat cortical neurons. Exposure to 100 microM glutamate for 5 h caused approximately 95% of the cultured neurons to die in 24 h. The NMDA-selective antagonist D-(-)-2-amino-5-phosphonopentanoate (APV) protected the neurons effectively when applied prior to or soon after glutamate treatment. However, infection with a viral vector expressing the proto-oncogene bcl-2 strongly protected neurons even if applied as late as 8 h following the glutamate insult. These data provides evidence that APV blocks an early stage of the death cascade in response to elevations of glutamate. By contrast bcl-2 appears to act at a fairly late stage in the cell death process and these results suggest a possible clinical role in treatment of ischemic brain disorders.