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
相关论文
共 70 条
[41]  
Martin-Villalba A, 1999, J NEUROSCI, V19, P3809
[42]   OVEREXPRESSION OF BCL-2 IN TRANSGENIC MICE PROTECTS NEURONS FROM NATURALLY-OCCURRING CELL-DEATH AND EXPERIMENTAL-ISCHEMIA [J].
MARTINOU, JC ;
DUBOISDAUPHIN, M ;
STAPLE, JK ;
RODRIGUEZ, I ;
FRANKOWSKI, H ;
MISSOTTEN, M ;
ALBERTINI, P ;
TALABOT, D ;
CATSICAS, S ;
PIETRA, C ;
HUARTE, J .
NEURON, 1994, 13 (04) :1017-1030
[43]   Pathophysiology of stroke: Lessons from animal models [J].
Mergenthaler, P ;
Dirnagl, U ;
Meisel, A .
METABOLIC BRAIN DISEASE, 2004, 19 (3-4) :151-167
[44]   NADPH-oxidase activity is elevated in penumbral and non-ischemic cerebral arteries following stroke [J].
Miller, Alyson A. ;
Dusting, Gregory J. ;
Roulston, Carli L. ;
Sobey, Christopher G. .
BRAIN RESEARCH, 2006, 1111 :111-116
[45]   Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke [J].
Morita-Fujimura, Y ;
Fujimura, M ;
Yoshimoto, T ;
Chan, PH .
STROKE, 2001, 32 (10) :2356-2361
[46]   Caspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia [J].
Mouw, G ;
Zechel, JL ;
Zhou, Y ;
Lust, WD ;
Selman, WR ;
Ratcheson, RA .
METABOLIC BRAIN DISEASE, 2002, 17 (03) :143-151
[47]  
Namura S, 1998, J NEUROSCI, V18, P3659
[48]  
OWENSCHAUB LB, 1995, MOL CELL BIOL, V15, P3032
[49]   Function of BID - a molecule of the bcl-2 family - in ischemic cell death in the brain [J].
Plesnila, N ;
Zinkel, S ;
Amin-Hanjani, S ;
Qiu, JH ;
Korsmeyer, SJ ;
Moskowitz, MA .
EUROPEAN SURGICAL RESEARCH, 2002, 34 (1-2) :37-41
[50]   Spatial resolution of phospholipid scramblase 1 (PLSCR1), caspase-3 activation and DNA-fragmentation in the human hippocampus after cerebral ischemia [J].
Rami, A ;
Sims, J ;
Botez, G ;
Winckler, J .
NEUROCHEMISTRY INTERNATIONAL, 2003, 43 (01) :79-87