Christensen Thomas, Bruhn Torben, Diemer Nils Henrik
Laboratory of Neuropathology, Institute of Molecular Pathology, University of Copenhagen, Frederik V's vej 11, 6th Floor, DK-2100 Copenhagen, Denmark.
Brain Res. 2003 Nov 14;990(1-2):66-76. doi: 10.1016/s0006-8993(03)03439-5.
The effect of the free radical spin-trap alpha-phenyl-butyl-tert-nitrone (alpha-PBN) in permanent focal cerebral ischemia in rats was examined in two series of experiments. In the first, rats were subjected to permanent occlusion of the middle cerebral artery (MCAO) and treated 1 h after occlusion with a single dose of alpha-PBN (100 mg/kg) or saline. Body temperature was measured and controlled for the first 24 h to obtain identical temperature curves in the two groups. Cortical infarct volumes were determined on histological sections 7 days later. alpha-PBN did not significantly reduce infarct volume (control: 28.3+/-16.3 mm3 vs. alpha-PBN 23.7+/-7.4 mm3). In the second series of experiments, periinfarct depolarizations (PIDs) were recorded with an extracellular DC electrode at two locations in the ischemic penumbra for the initial 3 h following MCAO. alpha-PBN (100 mg/kg, single dose in conjunction with occlusion) significantly reduced the total number (median value of 3 PIDs in the control groups vs. 1 PID in alpha-PBN groups, p<0.001) and total duration of the PIDs (median value 662 s in the control groups vs. 162 s in the alpha-PBN groups, p<0.006). In spite of this, cortical infarct volumes determined 7 days later in the same rats were not smaller in alpha-PBN-treated rats. The study thus demonstrates that attenuation of PIDs does not always lead to smaller infarcts if permanent arterial occlusion is followed by long survival time and does not support the hypothesis that PIDs per se are critical determinants of infarct size in this situation.
在两个系列的实验中，研究了自由基自旋捕捉剂α-苯基-叔丁基硝基酮（α-PBN）对大鼠永久性局灶性脑缺血的影响。在第一个实验中，对大鼠进行大脑中动脉永久性闭塞（MCAO），闭塞1小时后用单剂量的α-PBN（100mg/kg）或生理盐水治疗。在最初的24小时测量并控制体温，以使两组的体温曲线相同。7天后在组织学切片上测定皮质梗死体积。α-PBN并没有显著减小梗死体积（对照组：28.3±16.3mm³，α-PBN组：23.7±7.4mm³）。在第二个系列实验中，在MCAO后的最初3小时内，用细胞外直流电极在缺血半暗带的两个位置记录梗死周围去极化（PID）。α-PBN（100mg/kg，与闭塞同时给予单剂量）显著减少了PID的总数（对照组中PID的中位数为3次，α-PBN组为1次，p<0.001）和PID的总持续时间（对照组中位数为662秒，α-PBN组为162秒，p<0.006）。尽管如此，7天后在相同大鼠中测定的皮质梗死体积在α-PBN治疗组中并没有更小。因此，该研究表明，如果永久性动脉闭塞后存活时间较长，PID的减弱并不总是导致梗死面积减小，并且不支持在这种情况下PID本身是梗死面积关键决定因素的假设。
