Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain In Vivo Fluorescence Imaging
Dynamic Analysis of the Blood-Brain Barrier Disruption in Experimental Stroke Using Time Domain In Vivo Fluorescence Imaging
复制标题
DOI：
10.2310/7290.2008.00025
复制
发表时间：
2008-11-01
影响因子：
2.8
通讯作者：
Stanimirovic, Danica
中科院分区：
文献类型：
--
作者：
Abulrob, Abedelnasser;Brunette, Eric;Stanimirovic, Danica
脑缺血后血脑屏障（BBB）的破坏可用于将成像剂和治疗剂递送到脑中。本研究的目的是（a）建立新的体内光学成像方法，用于纵向评估BB B破坏和（B）评估短暂局灶性缺血后BB B破坏的尺寸选择性和时间模式。BBB渗透性在用游离Cy5.5（1 kDa）或Cy5.5与牛血清白蛋白（BSA）（67 kDa）缀合的对比增强后使用体内时域近红外光学成像在经受60或20分钟短暂大脑中动脉闭塞（MCAO）和不同时间的再灌注（长达14天）的小鼠中进行评估。通过离体脑成像和荧光示踪剂外渗的显微镜分析证实了体内成像观察结果。使用Cy 5. 5的体内光学对比度增强在空间上大于使用BSA-Cy 5.5所观察到的。短暂性20分钟MCAO后的纵向研究表明，双侧血脑屏障破坏，在同侧半球更明显，在缺血后第7天达到峰值，第14天消退。小分子和大分子的BBB破坏之间的面积差异可能潜在地用作替代成像标记物，用于评估可以递送适当大小的神经保护疗法的梗死周围组织。
The blood-brain barrier (BBB) disruption following cerebral ischemia can be exploited to deliver imaging agents and therapeutics into the brain. The aim of this study was (a) to establish novel In vivo optical imaging methods for longitudinal assessment of the BBB disruption and (b) to assess size selectivity and temporal patterns of the BBB disruption after a transient focal ischemia. The BBB permeability was assessed using in vivo time domain near-infrared optical imaging after contrast enhancement with either free Cy5.5 (1 kDa) or Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa) in mice subjected to either 60- or 20-minute transient middle cerebral artery occlusion (MCAO) and various times of reperfusion (up to 14 days). In vivo imaging observations were corroborated by ex vivo brain imaging and microscopic analyses of fluorescent tracer extravasation. The in vivo optical contrast enhancement with Cy5.5 was spatially larger than that observed with BSA-Cy5.5. Longitudinal studies after a transient 20-minute MCAO suggested a bilateral BBB disruption, more pronounced in the ipsilateral hemisphere, peaking at day 7 and resolving at day 14 after ischemia. The area differential between the BBB disruption for small and large molecules could potentially be useful as a surrogate imaging marker for assessing perinfarct tissues to which neuroprotective therapies of appropriate sizes could be delivered.