Toyoda T, Kassell N F, Lee K S
Department of Neurological Surgery, Virginia Neurological Institute, University of Virginia, Charlottesville, USA.
Neurosurgery. 1997 Feb;40(2):372-7; discussion 377-8. doi: 10.1097/00006123-199702000-00027.
Oxygen free radicals are considered important contributors to cerebral ischemia-reperfusion injury. The purpose of this study was to examine the effects of the hydroxyl radical scavenger, (+/-)-N, N'-propylenedinicotinamide (nicaraven), on cerebral injury after focal ischemia-reperfusion.
A total of 58 male Sprague-Dawley rats was subjected to transient focal ischemia by occluding both carotid arteries and one middle cerebral artery for 3 hours. Animals received continuous infusions of doses of 20 mg/kg per hour or 60 mg/kg per hour of nicaraven beginning either 10 minutes before (pretreatment) or immediately after (posttreatment) ischemia. Infarction volumes were evaluated by staining coronal brain sections with 2% 2,3,5-triphenyltetrazolium chloride (n = 40). In other animals (n = 18), brain edema was evaluated 1 hour after ischemia.
A dose of 20 mg/kg per hour of nicaraven elicited small reductions in infarction volume (14.7 and 12.3% for the pre- and posttreatment groups, respectively). Treatment with a dose of 60 mg/kg per hour of nicaraven provided significant reductions in the volume of infarction (18.6% [P < 0.05] and 20.9% [P < 0.01] reductions for the pre- and posttreatment groups, respectively). The reductions in infarction size did not differ significantly between the pre- and posttreatment groups receiving a dose of 60 mg/kg per hour of nicaraven. Posttreatment with either dose of nicaraven significantly reduced brain edema.
This study demonstrates the neuroprotective effects of a hydroxyl radical scavenger when administered systemically during the reperfusion phase after transient focal ischemia. The results provide, to our knowledge, the first evidence that nicaraven is effective against ischemia-reperfusion injury in the brain and demonstrate that oxygen free radicals generated during reperfusion are important triggers of ischemic brain damage. Furthermore, the findings suggest that nicaraven may be a useful agent in limiting brain injury after ischemic stroke.
氧自由基被认为是脑缺血再灌注损伤的重要促成因素。本研究的目的是检验羟自由基清除剂（±）-N，N'-亚丙基二烟酰胺（尼卡韦）对局灶性缺血再灌注后脑损伤的影响。
总共58只雄性Sprague-Dawley大鼠通过阻断双侧颈动脉和一条大脑中动脉3小时来进行短暂性局灶性缺血。动物在缺血前10分钟（预处理）或缺血后立即（后处理）开始以每小时20毫克/千克或每小时60毫克/千克的剂量持续输注尼卡韦。通过用2%的2,3,5-三苯基氯化四氮唑对冠状脑切片进行染色来评估梗死体积（n = 40）。在其他动物（n = 18）中，在缺血1小时后评估脑水肿。
每小时20毫克/千克剂量的尼卡韦使梗死体积略有减小（预处理组和后处理组分别减小14.7%和12.3%）。每小时60毫克/千克剂量的尼卡韦治疗使梗死体积显著减小（预处理组和后处理组分别减小18.6%[P < 0.05]和20.9%[P < 0.01]）。接受每小时60毫克/千克剂量尼卡韦的预处理组和后处理组之间梗死面积的减小没有显著差异。两种剂量的尼卡韦后处理均显著减轻脑水肿。
本研究证明了在短暂性局灶性缺血后的再灌注阶段全身给予羟自由基清除剂具有神经保护作用。据我们所知，结果首次证明尼卡韦对脑缺血再灌注损伤有效，并表明再灌注期间产生的氧自由基是缺血性脑损伤的重要触发因素。此外，研究结果表明尼卡韦可能是限制缺血性中风后脑损伤的有用药物。
