Polynitroxyl albumin reduces infarct size in transient focal cerebral ischemia in the rat:: Potential mechanisms studied by magnetic resonance imaging
Polynitroxyl albumin reduces infarct size in transient focal cerebral ischemia in the rat:: Potential mechanisms studied by magnetic resonance imaging
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DOI：
10.1097/00004647-199809000-00012
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发表时间：
1998-09-01
影响因子：
6.3
通讯作者：
Moseley, ME
中科院分区：
文献类型：
--
作者：
Beaulieu, C;Busch, E;Moseley, ME
已知氮氧自由基可保护细胞免受氧化损伤。应用磁共振弥散加权成像和灌注加权成像评价多硝酰白蛋白（PNA）对大鼠大脑中动脉腔内缝合局灶性脑缺血模型的影响。研究了三组Sprague-Dawley大鼠：（1）PNA（N = 6），（2）人血清白蛋白（N = 6），和（3）盐水（N = 7）。大脑中动脉闭塞2小时。诱导缺血后30分钟开始治疗。在三个时间点静脉内注射总剂量为1%体重（体积/重量）的PNA（23.5 mg/dL蛋白质和110 mmol/L氮氧化物）、白蛋白（23.5 mg/dL）或盐水：0.5小时时0.5%，2小时时0.25%（即，再灌注前）和闭塞后4小时的0.25%。在缺血2小时和再灌注2小时内采集6组弥散和灌注加权磁共振图像。在24小时处死大鼠，用氯化2，3，5-三苯基四唑（TTC）对脑进行染色。弥散加权成像显示，PNA治疗组的缺血性病变的生长受到抑制。PNA治疗组4小时弥散加权成像半球病变体积（25% +/- 9%）显著小于生理盐水治疗组（43% +/- 13%; P = 0.016）或白蛋白治疗组（38% +/- 6%; P = 0.017）。在PNA组（8% +/- 7%）、生理盐水组（35% +/- 8%; P < 0.001）和白蛋白组（31% +/- 6%; P <0.001）中，观察到24小时TTC衍生的病变体积存在较大差异。灌注加权成像显示，在缺血和再灌注过程中，PNA治疗组的脑灌注明显改善。总之，在大鼠短暂局灶性脑缺血模型中，用PNA治疗导致灌注改善和梗死体积减少。
Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin (PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA (N = 6), (2) human serum albumin (N = 6), and (3) saline (N = 7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging-derived hemispheric lesion volume in the PNA-treated group (25% +/- 9%) was significantly smaller than that in the saline-treated (43% +/- 13%; P = 0.016) or albumin-treated groups (38% +/- 6%; P = 0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8% +/- 7%), saline (35% +/- 8%; P < 0.001), and albumin (31% +/- 6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.