Apoptotic Mechanisms After Cerebral Ischemia

被引:1251
作者
Broughton, Brad R. S. [1 ]
Reutens, David C. [2 ]
Sobey, Christopher G. [1 ]
机构
[1] Monash Univ, Dept Pharmacol, Clayton, Vic 3800, Australia
[2] Monash Univ, So Clin Sch, Clayton, Vic 3800, Australia
基金
澳大利亚国家健康与医学研究理事会;
关键词
stroke; penumbra; caspases; cytochrome c; Fas receptor; NEURONAL CELL-DEATH; SUBSEQUENT DNA FRAGMENTATION; OXYGEN-GLUCOSE DEPRIVATION; MITOCHONDRIAL CYTOCHROME-C; TRANSIENT FOCAL ISCHEMIA; TRANSGENIC MICE PROTECTS; ARTERY OCCLUSION; BRAIN-INJURY; POLY(ADP-RIBOSE) POLYMERASE; NUCLEAR TRANSLOCATION;
D O I
10.1161/STROKEAHA.108.531632
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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. (Stroke. 2009; 40: e331-e339.)
引用
收藏
页码:E331 / E339
页数:9
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