A bcl-2 expressing viral vector protects cortical neurons from excitotoxicity even when administered several hours after the toxic insult.

The product of the bcl-2 oncogene has been shown to play an important role in apoptosis and programmed cell death. In this study, a herpes simplex virus type-1 vector was constructed to carry the human bcl-2 gene. The possible role of bcl-2 in protecting neurons from excitoxicity was investigated by using the viral vector to deliver the gene into neuronal cultures before or after the cells were exposed to glutamate under conditions in which 50-80% of neurons died. Infection with the bcl-2 expressing vector 24 h prior to glutamate treatment effectively prevented the cell death that normally follows this treatment. Moreover, infection with the vector as late as 8 h after the glutamate insult still resulted in substantial neuroprotective effects. These results have potential implications for new therapies in stroke or ischemic neuropathies.