Imperatore C, Germanò A, d'Avella D, Tomasello F, Costa G
Institute of Pharmacology, University of Messina, Italy.
Life Sci. 2000 Jan 21;66(9):779-90. doi: 10.1016/s0024-3205(99)00651-7.
Free radicals are important contributors to the global brain dysfunction that follows subarachnoid hemorrhage (SAH). We evaluated the effects of hydroxyl radical scavenger AVS [(+/-)-N,N'-propylenedinicotinamide; Nicaraven] after experimental SAH on rodent behavioral deficits (employing a battery of well-characterized assessment tasks over a 2-day observation period) and blood-brain barrier (BBB) permeability changes two days after SAH (quantifying the microvascular alterations according to the extravasation of protein-bound Evans Blue using a spectrophotofluorimetric technique) in dose-response and time-window experiments. Groups of 10 rats were injected with 400 microl of autologous blood into the cisterna magna, and followed by intravenous continuous infusion of saline or 0.1, 03 or 1 mg/kg/min of AVS beginning within 5 minutes or 6 or 12 hours after SAH. The results were compared with sham-operated saline-treated and with SAH saline-treated animals. AVS significantly ameliorated performances on Beam Balance (p < 0.01) and decreased BBB permeability changes in frontal, temporal, parietal, occipital and cerebellar cortices and subcortical and cerebellar nuclei and brainstem (p < 0.01), but did not significantly affect changes in Beam Walking. This study demonstrates the neuroprotective effects of AVS when administered after experimental SAH in rats. These effects were dose-dependent and, moreover, were evident within the therapeutic window of 6-12 hours after SAH. These results reinforce the concept of a participation of reactive oxygen intermediates in the cerebral dysfunction following SAH.
自由基是蛛网膜下腔出血（SAH）后导致全脑功能障碍的重要因素。我们评估了实验性SAH后给予羟基自由基清除剂AVS[（±）-N，N'-亚丙基二烟酰胺；烟浪丁]对啮齿动物行为缺陷（在2天观察期内采用一系列经过充分表征的评估任务）以及SAH后两天血脑屏障（BBB）通透性变化（使用分光荧光技术根据结合蛋白的伊文思蓝外渗情况量化微血管改变）的影响，进行了剂量反应和时间窗实验。将10只大鼠分为一组，向其脑大池内注射400微升自体血，然后在SAH后5分钟、6小时或12小时内开始静脉持续输注生理盐水或0.1、0.3或1毫克/千克/分钟的AVS。将结果与假手术生理盐水处理组以及SAH生理盐水处理组动物进行比较。AVS显著改善了横梁平衡实验中的表现（p<0.01），并降低了额叶、颞叶、顶叶、枕叶和小脑皮质以及皮质下和小脑核团及脑干的BBB通透性变化（p<0.01），但对横梁行走实验中的变化没有显著影响。本研究证明了实验性SAH后给予AVS对大鼠具有神经保护作用。这些作用具有剂量依赖性，而且在SAH后6 - 12小时的治疗窗内明显。这些结果强化了活性氧中间体参与SAH后脑功能障碍的概念。
