Pathophysiology of the ischemic penumbra - Revision of a concept
Pathophysiology of the ischemic penumbra - Revision of a concept
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DOI：
10.1023/a:1020265701407
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发表时间：
1998-12-01
影响因子：
4
通讯作者：
Back, T
中科院分区：
文献类型：
--
作者：
Back, T
1. 围绕密集脑缺血病灶的缺血半暗带的最初概念是基于电生理学观察。在大脑中动脉闭塞后的狒狒皮层中，在脑血流量（CBF）阈值水平约为100%时观察到皮层诱发电位完全失效。 0.15 ml/g/min——细胞外钾离子活性仅轻度升高的水平。当 CBF 减少到 0.06-0.10 ml/g/min 的范围时，细胞外钾发生大量增加，并与完全组织梗塞相关。因此，缺血半暗带被概念化为CBF减少已超过电功能失效阈值但未超过膜失效阈值的区域。2．最近的研究表明，传统上由血流阈值定义的半影不能在长时间的缺血中存活。 CBF放射自显影图与弥散加权MR图像以及脑代谢物的区域分布的相关性表明，当邻近的、以前的半影区域在血管闭塞的最初几个小时内经历不可逆的恶化时，缺血核心区域会扩大。同时，残留的半暗带变得仅限于缺血区域的外围，其命运可能很大程度上取决于早期的治疗干预。3。在脑梗塞的边缘区域，持续观察到局部 CBF 和葡萄糖利用的显着脱钩。与电生理学测量的相关性表明，代谢流解偶联与类似于瞬时去极化的直流电（DC）电势的持续偏转相关。这种半影细胞去极化与代谢负荷增加有关，由于侧支血流受限而诱发组织缺氧，刺激无氧糖酵解导致乳酸中毒，抑制蛋白质合成，最后损害能量代谢。它们发生的频率与缺血性损伤的最终体积相关。因此，半影去极化被认为是缺血性脑损伤发病机制中的关键事件。 NMDA 和非 NMDA 拮抗剂可抑制梗塞周围 DC 偏转，从而显着减小梗塞面积。4．半暗带内的组织病理学后遗症包括不同程度的分散性神经元损伤，也称为“不完全梗死”。梗塞边界神经元密度的降低是一种血流和时间依赖性事件，伴随着神经胶质细胞的早期反应。早在血管闭塞后 3 小时，即可在整个同侧皮层检测到普遍的小胶质细胞激活。从闭塞后 6 小时起，在缺血半球的完整部分观察到星形胶质细胞活化。因此，半暗带是一个活力有限的空间动态大脑区域，其特征是复杂的病理生理变化，涉及神经元功能以及响应局部缺血性损伤的神经胶质激活。
1. The original concept of the ischemic penumbra surrounding a focus of dense cerebral ischemia is based on electrophysiological observations. In the cortex of baboons following middle cerebral artery occlusion, complete failure of the cortical evoked potential was observed at a cerebral blood flow (CBF) threshold level of approx. 0.15 ml/g/min-a level at which extracellular potassium ion activity was only mildly elevated. With a greater CBF decrement to the range of 0.06-0.10 ml/g/min, massive increases in extracellular potassium occurred and were associated with complete tissue infarction. Thus, the ischemic penumbra has been conceptualized as a region in which CBF reduction has exceeded the threshold for failure of electrical function but not that for membrane failure.2. Recent studies demonstrate that the penumbra as defined classically by the flow thresholds does not survive prolonged periods of ischemia. The correlation of CBF autoradiograms with diffusion-weighted MR images and the regional distribution of cerebral metabolites reveals that the ischemic core region enlarges when adjacent, formerly penumbral, areas undergo irreversible deterioration during the initial hours of vascular occlusion. At the same time, the residual penumbra becomes restricted to the periphery of the ischemic territory, and its fate may depend critically upon early therapeutic intervention.3. In the border zone of brain infarcts, marked uncoupling of local CBF and glucose utilization is consistently observed. The correlation with electrophysiological measurements shows that metabolism-flow uncoupling is associated with sustained deflections of the direct current (DC) potential resembling transient depolarizations. Such penumbral cell depolarizations, which are associated with an increased metabolic workload, induce episodes of tissue hypoxia due to the constrained collateral flow, stimulate anaerobic glycolysis leading to lactacidosis, suppress protein synthesis, and, finally, compromise energy metabolism. The frequency of their occurrence correlates with the final volume of ischemic injury. Therefore, penumbral depolarizations are regarded as a key event in the pathogenesis of ischemic brain injury. Periinfarct DC deflections can be suppressed by NMDA and non-NMDA antagonists, resulting in a significant reduction of infarct size.4. The histopathological sequelae within the penumbra consist of Various degrees of scattered neuronal injury, also termed "incomplete infarction." The reduction of neuronal density at the infarct border is a flow- and time-dependent event which is accompanied by an early response of glial cells. As early as 3 hr after Vascular occlusion a generalized microglial activation can be detected throughout the ipsilateral cortex. Astrocytic activation is observed in the intact parts of the ischemic hemisphere from 6 hr postocclusion onward. Thus, the penumbra is a spatially dynamic brain region of limited viability which is characterized by complex pathophysiological changes involving neuronal function as well as glial activation in response to local ischemic injury.