Apoptotic neuronal death following cerebral ischaemia

Transient cerebral ischaemia accompanies a number of disease processes, including stroke, subarachnoid haemorrhage and head injury, that have a profound social and economic impact on our community. The development of neuroprotective agents that reduce the morbidity associated with these diverse conditions requires an understanding of the mechanisms of neuronal death following cerebral ischaemia. There is increasing evidence that a significant proportion of neurons die following ischaemia by a process called apoptosis. Apoptosis involves the activation of a highly regulated series of intracellular events in which the neuron actively participates in its own death. Genes such as bcl-2 and proteolytic enzymes such as the caspases, which have been shown to play an important role in apoptotic cell death in other cell types, are now being investigated for their role in apoptotic neuronal death. This review will focus on current knowledge of the intracellular pathways of apoptosis, with particular reference to their role in ischaemic neuronal death.