Electrochemical Failure of the Brain Cortex Is More Deleterious When it Is Accompanied by Low Perfusion
Electrochemical Failure of the Brain Cortex Is More Deleterious When it Is Accompanied by Low Perfusion
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DOI：
10.1161/strokeaha.112.660589
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发表时间：
2013-02-01
期刊：
影响因子：
8.3
通讯作者：
Priller, Josef
中科院分区：
文献类型：
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作者：
Dreier, Jens P.;Victorov, Ilya V.;Priller, Josef
背景和目的-临床和实验证据表明，当扩散除极持续时间超过特定时间点(称为承诺点)时，扩散性去极化有助于神经元损伤。方法：采用大鼠颅窗模型，观察脑电生理和脑血流的变化，并对皮质损伤进行组织学和免疫组织化学分析。结果：在第一组中，脑局部应用高K+浓度的人工脑脊液(ACSF)1小时，可以诱导固定持续时间的去极化事件，脑血流在基线附近波动(短暂的初始低灌流后充血)。在第2组中，非清道夫血红蛋白([HB](ACSF))和高[K+](ACSF)共同应用导致类似持续时间的去极化事件，伴随着严重的灌流不足(=扩散性缺血)。在第3组，静脉注射L钙通道拮抗剂尼莫地平和脑局部应用高[K+](ACSF)/[Hb](ACSF)使扩张性缺血恢复为扩张性充血。而第1组和第3组皮质浅层可见散在神经元损伤，第2组可见各层坏死，组织结构部分丧失，小胶质细胞活化。结论低灌注区皮质电化学性损伤更为严重。因此，皮质的承诺点不是一个普适值，而是取决于其他因素，如灌注度。(笔划。2013；44：490-496。)
Background and Purpose-Clinical and experimental evidence suggests that spreading depolarization facilitates neuronal injury when its duration exceeds a certain time point, termed commitment point. We here investigated whether this commitment point is shifted to an earlier period, when spreading depolarization is accompanied by a perfusion deficit.Methods-Electrophysiological and cerebral blood flow changes were studied in a rat cranial window model followed by histological and immunohistochemical analyses of cortical damage.Results-In group 1, brain topical application of artificial cerebrospinal fluid (ACSF) with high K+ concentration ([K+](ACSF)) for 1 hour allowed us to induce a depolarizing event of fixed duration with cerebral blood flow fluctuations around the baseline (short-lasting initial hypoperfusions followed by hyperemia). In group 2, coapplication of the NO-scavenger hemoglobin ([Hb](ACSF)) with high [K+](ACSF) caused a depolarizing event of similar duration, to which a severe perfusion deficit was coupled (=spreading ischemia). In group 3, intravenous coadministration of the L-type calcium channel antagonist nimodipine with brain topical application of high [K+](ACSF)/[Hb](ACSF) caused spreading ischemia to revert to spreading hyperemia. Whereas scattered neuronal injury occurred in the superficial cortical layers in the window areas of groups 1 and 3, necrosis of all layers with partial loss of the tissue texture and microglial activation were observed in group 2.Conclusions-The results suggest that electrochemical failure of the cortex is more deleterious when it is accompanied by low perfusion. Thus, the commitment point of the cortex is not a universal value but depends on additional factors, such as the level of perfusion. (Stroke. 2013;44:490-496.)