[Apoptosis in focal brain ischemia].
[Apoptosis in focal brain ischemia].
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发表时间：
2003-07
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通讯作者：
Z. Zador;Z. Lacza;Z. Benyó;T. Harkany;T. Hortobágyi
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作者：
Z. Zador;Z. Lacza;Z. Benyó;T. Harkany;T. Hortobágyi
在发达国家，缺血性中风是导致死亡和残疾的主要原因之一。它是由脑血流的局灶性损害引起的。随后的缺血性细胞死亡本质上主要是坏死性的。然而，一个重要的治疗特征是原发灶核心边缘区域的凋亡细胞死亡延迟。细胞凋亡是当前医学和生物学研究的热点领域之一。对其机制的更好理解可能为包括缺血性中风在内的多种疾病的治疗提供新的和更有效的方法。总结了局灶性脑缺血的显著神经学特征以及凋亡和坏死性细胞死亡的形态特征。对细胞凋亡的机制进行了讨论。它被分为决策的早期遗传阶段和随后的细胞执行阶段。讨论了促和抗凋亡基因及其蛋白产物微调平衡的早期转变的特征，在此之前是细胞内离子钙稳态失衡、能量耗竭和线粒体功能障碍。强调了半胱氨酸氨基转移酶在细胞凋亡中的重要作用。三种可能的途径在执行阶段被描述：内在的和外在的caspase激活级联和caspase非依赖性的细胞内信号转导途径。讨论了执行阶段神经细胞膜损伤的分子机制，并给出了一些改变蛋白质合成的例子，也称为消息选择。强调了晚期再灌流在执行阶段的重要作用。介绍了抗细胞凋亡治疗方法的可能靶点和实验研究的结果，并展望了它们在人类临床护理中的应用前景。
Ischaemic stroke is one of the major causes of death and disability in the developed world. It is caused by focal impairment of cerebral blood flow. The subsequent ischaemic cell death is predominantly necrotic in nature. However, a therapeutically important characteristic is the delayed apoptotic cell demise in the border zone of the primary lesion core. Apoptosis is one of the most intensively studied field of current medical and biological research. The better understanding of its mechanism may provide novel and more effective ways of therapy in a wide range of diseases including ischemic stroke. The salient neurological features of focal brain ischaemia and the morphological signs of apoptotic and necrotic cell death are summarized. The mechanism of apoptosis is discussed. It is divided into an early genetic phase of decision-making followed by a cellular execution phase. The characteristics of the early shift in the finely tuned balance of pro- and antiapoptotic genes and their protein products, which is preceded by an inbalance in intracellular ionized calcium homeostasis, energy depletion and mitochondrial dysfunction is discussed. The crucial role of caspases in apoptosis is emphasized. The three possible pathways during the execution phase is described: the intrinsic- and extrinsic caspase activation cascade and the caspase-independent intracellular signal transduction route. The molecular mechanism of neural cell membrane damage in the execution phase is discussed and some examples of altered protein synthesis also known as message-selection are given. The important role of late reperfusion in the execution phase is emphasized. The possible targets of antiapoptotic therapeutic approaches and the results of experimental studies are presented as well as the perspectives of their use in human clinical care.