Abulrob Abedelnasser, Brunette Eric, Slinn Jacqueline, Baumann Ewa, Stanimirovic Danica
Institute for Biological Sciences, National Research Council of Canada, Ottawa, ON, Canada.
Methods Mol Biol. 2011;763:423-39. doi: 10.1007/978-1-61779-191-8_29.
The blood-brain barrier (BBB) disruption following cerebral ischemia (stroke) contributes to the development of life-threatening brain edema. Recent studies suggested that the ischemic BBB disruption is not uniform throughout the affected brain region. The aim of this study was to establish in vivo optical imaging methods to assess the size selectivity and spatial distribution of the BBB disruption after a focal cerebral ischemia. The BBB permeability was assessed in mice subjected to a 60-min middle cerebral artery occlusion and 24 h of reperfusion using in vivo time domain near-infrared optical imaging after contrast enhancement with two tracers of different molecular size, Cy5.5 (1 kDa) and Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa). Volumetric reconstruction of contrast-enhanced brain areas in vivo and ex vivo indicated that the BSA-Cy5.5-enhancement is identical to the volume of infarct determined by TTC staining, whereas the volume of enhancement with Cy5.5 was 40% greater. The volume differential between areas of BBB disruption for small and large-size molecules could be useful for determining the size of peri-infarct tissues (penumbra) that can respond to neuroprotective therapies.
脑缺血（中风）后血脑屏障（BBB）的破坏会导致危及生命的脑水肿的发展。最近的研究表明，缺血性血脑屏障破坏在整个受影响的脑区并不均匀。本研究的目的是建立体内光学成像方法，以评估局灶性脑缺血后血脑屏障破坏的大小选择性和空间分布。在使用两种不同分子大小的示踪剂（Cy5.5（1 kDa）和与牛血清白蛋白（BSA）偶联的Cy5.5（67 kDa））进行对比增强后，通过体内时域近红外光学成像评估了经历60分钟大脑中动脉闭塞和24小时再灌注的小鼠的血脑屏障通透性。体内和体外对比增强脑区的体积重建表明，BSA-Cy5.5增强与TTC染色确定的梗死体积相同，而Cy5.5增强的体积大40%。小分子和大分子血脑屏障破坏区域之间的体积差异可能有助于确定可对神经保护疗法作出反应的梗死周围组织（半暗带）的大小。
