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【Brain】选择性神经元缺失影响缺血半暗带并可能
Selective neuronal loss in rescued penumbra relates to initial hypoperfusion
Selective neuronal loss (SNL) in the rescued penumbra could account for suboptimal clinical recovery despite effective early reperfusion. Previous studies of SNL used single-photon emission tomography (SPECT), did not account for potential volume loss secondary to collapse of the infarct cavity, and failed to show a relationship with initial hypoperfusion. Here, we obtained acute-stage computerized tomography (CT) perfusion and follow-up quantitative 11C-flumazenil (FMZ)-PET to map SNL in the non-infarcted tissue and assess its relationship with acute-stage hypoperfusion. We prospectively recruited seven patients with evidence of acute (<6 h) extensive middle cerebral artery territory ischaemia based on clinical deficit (National Institutes of Health stroke scale, NIHSS score range: 8–23) and CT Perfusion (CTp) findings and (ii) early recanalization (spontaneous or following thrombolysis) based on spectacular clinical recovery ( NIHSS 6 at 24 h), good clinical outcome (NIHSS 5) and small final infarct (6/7 subcortical) on late-stage MRI. Ten age-matched controls were also studied. FMZ image analysis took into account potential post-stroke volume loss. Across patients, clusters of significantly reduced FMZ binding were more prevalent and extensive in the non-infarcted middle cerebral artery cortical areas than in the non-affected hemisphere (P = 0.028, Wilcoxon sign rank test). Voxel-based between-group comparisons revealed several large clusters of significantly reduced FMZ binding in the affected peri-insular, superior temporal and prefrontal cortices (FDR P < 0.05), as compared with no cluster on the unaffected side. Finally, comparing CTp and PET data revealed a significant negative correlation between FMZ binding and initial hypoperfusion. Applying correction for volume loss did not substantially alter the significance of these results. Although based on a small patient sample sometimes studied late after the index stroke, and as such preliminary, our results establish the presence and distribution of FMZ binding loss in ultimately non-infarcted brain areas after stroke. In addition, the data suggest that this binding loss is proportional to initial hypoperfusion, in keeping with the hypothesis that the rescued penumbra is affected by SNL. Although its clinical counterparts remain uncertain, it is tempting to speculate that peri-infarct SNL could represent a new therapeutic target.
译文：缺血半暗带中选择性的神经元缺失（SNL）可以解释早期有效再关注后次最佳临床恢复的原因。既往SNL的研究使用SPECT技术并无法计入继发于梗死中心区结构坍塌后潜在的神经元丢失，因而无法显示SNL与灌注不足初期的关系。在本研究中，我们通过得到的急性期CT灌注扫描图象和11C氟马西尼定量示踪PET（FMZ）图象勾画非梗死组织中的SNL图，同时评估SNL与灌注不足急性期之间的关系。我们前瞻性的纳入7名患者，他们符合以下纳入标准：（1）急性的大脑中动脉区域广泛缺血（起病小于6h）：临床神经缺损评分NIHSS 8－23分且具有CT灌注扫描（CTp）支持的依据；（2）早期血管再通（自发性或溶栓后再通）：临床恢复明显，临床神经功能评分明显改善（NIHSS no more than 5），后期MRI显示大多为小型终末梗死。同时纳入10例年龄匹配的对照。FMZ图象分析将卒中后潜在的脑组织缺失也包括进来。患者自身横向对比分析显示，较未发生缺血的半球而言，存在大脑中动脉缺血的半球的皮质未梗死区，其减少的FMZ簇更加普遍，也更加弥散。组间容量成分CT显影的对比显示脑岛周围、颞叶顶部和前额部皮质较对侧半球存在几个较大的具有显著意义的下降的FMZ簇。最后，CTp和PET的对比显示FMZ束和灌注不足早期之间存在显著的负相关。应用组织缺失容积的校正不能从实质上改变上述结果的显著性。本研究虽然是基于经典卒中后的小样本研究，即前驱性研究，但研究结果仍然证实了卒中后非梗死区域FMZ簇的存在与分布。此外，研究数据还表明FMZ簇的丢失与早期灌注不足呈比例关系，进而支持缺血半暗带的范围受SNL影响这一假说。尽管这一假说对应的临床病理过程尚不确定，但它所设想的环梗死区SNL却可能成为一种新的治疗靶点。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-06-15 05:14
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