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(Stroke. 2009;40:e331.)
© 2009 American Heart Association, Inc.

Comments, Opinions, and Reviews

Apoptotic Mechanisms After Cerebral Ischemia

From the Department of Pharmacology (B.R.S.B., C.G.S.), Monash University, Victoria, Australia; and the Southern Clinical School (D.C.R.), Monash University, Clayton, Australia.

Correspondence to Christopher G. Sobey, PhD, Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia. E-mail chris.sobey{at}med.monash.edu.au

Background and Purpose— 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.

Summary of Review— 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.

Key Words: stroke • penumbra • caspases • cytochrome c • Fas receptor