The two pathophysiologies of focal brain ischemia: implications for translational stroke research
The two pathophysiologies of focal brain ischemia: implications for translational stroke research
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DOI：
10.1038/jcbfm.2011.186
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发表时间：
2012-07-01
影响因子：
6.3
通讯作者：
Hossmann, Konstantin-Alexander
中科院分区：
文献类型：
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作者：
Hossmann, Konstantin-Alexander
局灶性脑缺血后的脑损伤沿着两种基本不同的病理生理机制发展，这取决于主要血流减少的严重程度和缺血后再循环的动力学。在永久性和渐进性逆转的局灶性缺血中，如血栓栓塞术后，原发核心损伤是不可逆的，但核心向半影区的扩张可以通过血流动力学和分子干预来缓解。这种缓解只能在缺血发作后3小时内实现，因为在这段时间内，未经治疗的核心损伤会扩大到接近最大尺寸。在短暂性脑缺血后迅速逆转的情况下，如机械血管闭塞后，原发核心损伤可恢复，但继发迟发性损伤在长达6~12小时的自由间隔后演变。这种损伤可以在整个自由间期内减轻，但较长的窗口没有临床意义，因为暂时性机械性血管闭塞不是自然发生的中风模型。由于这种差异在中风研究中被广泛忽视，大多数临床试验都被设计成过长的治疗窗口，这就是它们失败的原因。因此，暂时性机械性血管闭塞模型应从临床前卒中研究中剔除。《脑血流与代谢杂志》(2012年)32期，1310-1316年；doi：10.1038/jcbfm.2011.186；2012年1月11日在线发布
Brain injury after focal ischemia evolves along two basically different pathophysiologies, depending on the severity of the primary flow reduction and the dynamics of postischemic recirculation. In permanent and gradually reversed focal ischemia as after thromboembolic occlusion, primary core injury is irreversible but the expansion of the core into the penumbra can be alleviated by hemodynamic and molecular interventions. Such alleviation can only be achieved within 3 hours after the onset of ischemia because untreated core injury expands to near maximum size during this interval. In promptly reversed transient ischemia as after mechanical vascular occlusion, primary core injury may recover but a secondary delayed injury evolves after a free interval of as long as 6 to 12 hours. This injury can be alleviated throughout the free interval but the longer window is without clinical relevance because transient mechanical vascular occlusion is not a model of naturally occurring stroke. As this difference is widely ignored in stroke research, most clinical trials have been designed with a far too long therapeutic window, which explains their failure. Transient mechanical vascular occlusion models should, therefore, be eliminated from the repertoire of preclinical stroke research. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1310-1316; doi: 10.1038/jcbfm.2011.186; published online 11 January 2012