title: Apoptotic mechanisms after cerebral ischemia.
abstract: OBJECTIVE
  Traditionally, cell death after cerebral ischemia was considered to be exclusively necrotic in nature, but research over the past decade has revealed that after a stroke, many neurons in the ischemic penumbra will undergo apoptosis.
  
  
  RESULTS
  This brief review provides a general overview and update of various signaling pathways in the development of apoptosis in ischemic lesions. Cerebral ischemia triggers two general pathways of apoptosis: the intrinsic pathway, originating from mitochondrial release of cytochrome c and associated stimulation of caspase-3; and the extrinsic pathway, originating from the activation of cell surface death receptors, resulting in the stimulation of caspase-8. Although many of the key apoptotic proteins have been identified, our understanding of the complex underlying mechanisms remains poor and hence treatment of stroke patients by manipulating apoptotic pathways remains a daunting task. However, recent advances in the field have helped broaden our knowledge of apoptosis after cerebral ischemia. Further to the simplistic concept that stroke-induced apoptosis occurs predominantly in neurons and is caspase-dependent, accumulating evidence now indicates that apoptosis is prevalent in nonneuronal cells and that caspase-independent mechanisms also play a key role.
  
  
  CONCLUSIONS
  Although the ischemic penumbra is under threat of infarction, it is potentially salvageable and thus represents an opportunity for therapeutic intervention.
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: Brad R S
authors.initials: BR
authors.lastname: Broughton
authors.forename: David C
authors.initials: DC
authors.lastname: Reutens
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020169:Caspases / Q000502:physiology; D004249:DNA Damage; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D015220:Calcium Channels; D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D020169:Caspases; D002118:Calcium