Smith Wade S
Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143-0114, USA.
J Vasc Interv Radiol. 2004 Jan;15(1 Pt 2):S3-12. doi: 10.1097/01.rvi.0000108687.75691.0c.
The pathophysiology of cerebral ischemia is best understood in animal models of stroke. Within minutes of interrupted blood flow, mitochondria are deprived of substrate, which prevents adenosine triphosphate generation and results in membrane depolarization. This leads to increased intracellular calcium and sodium concentration followed by generation of free radicals and initiation of apoptosis. Glutamate release from ischemic neurons contributes to cellular damage. Each step in this complex, interdependent series of events offers a potential point to intervene and prevent neuronal death. Although many human trials in acute stroke therapy have had disappointing results, many promising therapies are in the pipeline, including hypothermia and free-radical inhibitors. Herein, the author discusses the pathophysiology of focal cerebral ischemia as has been revealed in rodent models and reviews the major human trials according to treatment mechanism.
脑缺血的病理生理学在中风动物模型中得到了最好的理解。在血流中断后的几分钟内，线粒体被剥夺底物，这阻止了三磷酸腺苷的生成并导致膜去极化。这会导致细胞内钙和钠浓度增加，随后产生自由基并引发细胞凋亡。缺血神经元释放的谷氨酸会导致细胞损伤。这一系列复杂且相互依存的事件中的每一步都提供了一个潜在的干预点，以防止神经元死亡。尽管许多急性中风治疗的人体试验结果令人失望，但许多有前景的疗法正在研发中，包括低温疗法和自由基抑制剂。在此，作者讨论了啮齿动物模型中所揭示的局灶性脑缺血的病理生理学，并根据治疗机制回顾了主要的人体试验。
