IN-VIVO MAPPING OF BRAIN BENZODIAZEPINE RECEPTOR CHANGES BY POSITRON EMISSION TOMOGRAPHY AFTER FOCAL ISCHEMIA IN THE ANESTHETIZED BABOON
IN-VIVO MAPPING OF BRAIN BENZODIAZEPINE RECEPTOR CHANGES BY POSITRON EMISSION TOMOGRAPHY AFTER FOCAL ISCHEMIA IN THE ANESTHETIZED BABOON
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DOI：
10.1161/01.str.24.12.2046
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发表时间：
1993-12-01
期刊：
影响因子：
8.3
通讯作者：
MACKENZIE, ET
中科院分区：
文献类型：
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作者：
SETTE, G;BARON, JC;MACKENZIE, ET
背景和目的：最近的报告显示，在实验动物和人体中，[H-3]PK 11195与外周型苯二氮卓类受体的特异性结合（体外）增加，反映了局灶性缺血损伤内和周围的神经胶质/巨噬细胞反应。我们已经评估了由正电子发射断层扫描的时间过程中的变化，在体内的C-11标记的PK 11195和氟马西尼（中枢苯二氮卓类受体拮抗剂）作为间接和直接标记的神经元损失，分别局灶性脑缺血后的脑摄取。10只麻醉狒狒在单侧大脑中动脉闭塞后第1天和第91天之间进行了连续的正电子发射断层扫描研究。这些研究包括在相同的正电子发射断层扫描阶段连续评估[C-11]PK 11195、[C-11]氟马西尼、脑血流量和耗氧量;获得晚期计算机断层扫描以绘制梗死的近似轮廓并定义同心圆梗死周围区域。我们发现梗死周围区域的[C-11]PK 11195摄取呈显著的时间依赖性增加，在闭塞后20 - 40天达到最大值。相比之下，梗死区[C-11]氟马西尼摄取出现时间和灌注依赖性显著降低，从第2天开始稳定，并且在第1天已经存在于一只狒狒中。饱和剂量冷配体的挑战研究证实，这些变化代表了特异性结合的改变。[C-11]在低代谢组中，氟马西尼摄取不受影响。（但显然未梗塞，即去传入）皮质区域。结论：体内[C-11]PK 11195特异性吸收的延迟和明显短暂的增加可能代表胶质细胞/巨噬细胞反应;[C-11]氟马西尼特异性结合的显著抑制，其似乎对突触损伤具有选择性，是早熟的和持续的，因此可能更适合于人类缺血性损伤的早期评估。
Background and Purpose: Recent reports have shown an increase in specific binding (in vitro) of [H-3]PK 11195 to peripheral-type benzodiazepine receptors in both experimental animals and humans, reflecting a glial/macrophagic reaction within and around focal ischemic insults. We have evaluated by positron emission tomography the time course of changes in brain uptake in vivo of C-11-labeled PK 11195 and flumazenil (an antagonist of central benzodiazepine receptors) as indirect and direct markers of neuronal loss, respectively, after focal cerebral ischemia.Methods. Ten anesthetized baboons were submitted to sequential positron emission tomography studies between day 1 and day 91 after unilateral middle cerebral artery occlusion. The studies consisted of successive assessments, in the same positron emission tomography session, of [C-11]PK 11195, [C-11]flumazenil, cerebral blood flow, and oxygen consumption; late computed tomographic scans were obtained to map the approximate contours of infarction and to define a concentric peri-infarct area.Results: We found a significant time-dependent increase in [C-11]PK 11195 uptake in the peri-infarcted area, maximum at 20 to 40 days after occlusion. In contrast, there was a time- and perfusion-independent significant decrease in [C-11]flumazenil uptake in the infarcted area, stable from day 2 onward, and already present in one baboon at day 1. Challenge studies with saturating doses of cold ligands confirmed that these changes represented alterations in specific binding. [C-11]Flumazenil uptake was not affected in hypometabolic (but apparently noninfarcted, ie, deafferented) cortical areas.Conclusions: The delayed and apparently transient increases in [C-11]PK 11195 specific uptake in vivo presumably represent glial/macrophage reaction; the marked depression in [C-11]flumazenil specific binding, which appears selective for synaptic damage, is both precocious and sustained and thus may be better suited for the early assessment of ischemic damage in humans.