Experiments with transgenic mice and gene manipulations are used to decipher a possible role for neuronal apoptosis after cerebral ischemia. Bcl-2 overexpression in transgenic mice reduces hippocampal pyramidal neuron degeneration after global ischemia (175). However, the effect of Bcl-2 transgene expression cannot yet be ascribed specifically to antiapoptotic activity, because this protein has additional functions in injured neurons, including axonal regeneration (176) and blocking the release of calcium from the ER (177). Drug-induced and virally mediated overexpression of NAIP also protects CAI neuron degeneration after global ischemia (178), but it is still not certain whether this protection results directly from blocking apoptotic mechanisms in CAI pyramidal neurons. These manipulations could protect or alter the functioning of neurons (e.g., interneurons or upstream presynaptically-coupled neurons) other than CAI pyramidal neurons that then protect against GluR-mediated excitotoxic neuronal death of CAI neurons.