MRI INVEST OF POLYNITROXYL ALBUMIN IN TRANSIENT FOCAL CEREBRAL ISCHEMIA IN RAT

简介：弥散加权(DWI)和灌注加权(PWI) 磁共振成像是评估疾病的有力工具 治疗中风的药物。时间上的进程 DWI可监测缺血性损害，而PWI可用于 追踪潜在的血流动力学。这项研究的目的是 评价一种新型血管内化合物--多硝基的疗效 白蛋白(PNA)(SynZyme Technologies)，在短暂局灶性脑损伤中 建立大鼠脑缺血模型。方法：麻醉SD大鼠 大鼠大脑中动脉闭塞(MCAO)2小时。 腔内缝合。3个处理组(每组6只) 研究：I)生理盐水和II)白蛋白作为对照，III)PNA。PNA， 静脉注射白蛋白或生理盐水。在大脑中动脉阻塞后0.5、2和4小时 (总剂量=体重的1%)。DWI和PWI(团注跟踪) 在GE CSI 2T光谱仪上进行，温度为0.25(第一种药物之前 治疗)、MCAO后1、1.7、2.3、3、4h。在24小时内，大脑 切片用2，3，5-三苯基四氮唑(TTC)染色 以获得一种不依赖于MRI的缺血性损伤测量方法。结果和 结论：弥散张量成像对缺血区的监测能力强。 时间显示了不同的进化模式。病变体积增加 对盐水组和白蛋白组都有显著影响，而 PNA组皮损生长受到抑制。病变 PNA组的容量(4hDWI)比对照组减少了63% 生理盐水组(p=0.003)，与白蛋白组相比增加了52%(p= 0.006)。TTC衍生的损伤体积在24小时内是合理的 在4小时内与DWI一致。血流灌注测量表明 再灌流前后血流的改善可能是 PNA的有益作用。

Introduction: Diffusion- (DWI) and perfusion-weighted (PWI) magnetic resonance imaging are powerful tools for the evaluation of therapeutic drugs for stroke. The temporal progression of the ischemic lesion can be monitored by DWI whereas PWI can be used to follow the underlying hemodynamics. The purpose of this study was to evaluate the efficacy of a novel intra-vascular compound, polynitroxyl albumin (PNA) (SynZyme Technologies), in a transient focal cerebral ischemia model in the rat. Methods: Anesthetized Sprague-Dawley rats underwent 2 hours of middle cerebral artery occlusion (MCAO) by an intraluminal suture. Three treatment groups (N=6 per group) were studied: i) saline and ii) albumin as controls, and iii) PNA. PNA, albumin, or saline was injected i.v. at 0.5, 2, and 4 h post-MCAO (total dose = 1% body weight). DWI and PWI (bolus tracking) were performed on a GE CSI 2 T spectrometer at 0.25 (before first drug treatment), 1, 1.7, 2.3, 3, and 4 h post-MCAO. At 24 h, brain sections were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to obtain an MRI-independent measure of ischemic injury. Results and Conclusion: The ability of DWI to monitor the ischemic region over time revealed different evolution patterns. Lesion volumes increased significantly for both the saline- and albumin groups, whereas the growth of the lesion was suppressed in the PNA group. The lesion volume (4 h DWI) in the PNA group was reduced by 63% compared to the saline group (p=0.003) and by 52% compared to the albumin group (p = 0.006). The TTC-derived lesion volumes at 24 h are in reasonable agreement with the DWI at 4 h. The perfusion measurements suggest that improved blood flow pre- and post-reperfusion may be responsible for the beneficial effect of PNA.