The death of granule neurons after ischemia may have more than one trigger. Granule ne; ron apoptosis may be a direct consequence of the HI. Alternatively, it may be secondary to degeneration of hippocampal pyramidal neurons and cerebellar Purkinje cells and is a form of target deprivation-induced apoptosis, similar to thalamic neuron death after cortical lesions (8,180,181) and motor neuron degeneration after axotomy (116,118). We know that the distribution of brain damage after HI follows a connectivity related distribution (182). The apoptosis of granule neurons is consistent with this idea and may possibly explain the contradictory evidence for apoptosis in hippocampal pyramidal neurons found in homogenate-based biochemical experiments.