Tasdemiroglu E, Christenberry P D, Ardell J L, Chronister R B, Taylor A E
Department of Surgery, University of Kentucky Chandler Medical Center, Lexington, USA.
Acta Neurochir (Wien). 1994;131(3-4):302-9. doi: 10.1007/BF01808631.
The role of free oxygen radicals in blood-brain barrier (BBB) disruption and postischemic hyperemia was evaluated in the rabbit model of focal cerebral ischemia-reperfusion. Six groups of rabbits underwent clipping of the anterior cerebral, middle cerebral, and intracranial internal carotid arteries. Cerebral blood flow (CBF) was measured by using radiolabeled microspheres, before, during, and 15 minutes after 1-hour occlusion of these arteries. After 50 minutes of ischemia, Group 1 animals (control) received a placebo. Animals in Groups 2-4 received one of three drugs: catalase at 10 mg/kg, methimazole at 5 mg/kg, or indomethacin at 10 mg/kg. A fifth group received a tungsten-supplemented diet for 14 days before ischemia was induced, and a sixth group was sham operated. Microvascular integrity within the brain was determined by the presence or absence of Evan's Blue (EB)-albumin dye leakage across the BBB and was measured by microspectrofluorometry. In the control group during ischemia, CBF dropped to 14%, 7%, and 11% of preischemic levels in rostral, middle, and caudal sections of the brain, respectively, as characterized by extensive EB-albumin dye leakage through the BBB into the ischemic hemisphere. During early reperfusion, postischemic hyperemia was associated with an increase in CBF of 128%, 123%, and 129% of control in the rostral, middle, and caudal sections of the brain, respectively. In all treated groups and in the group receiving a tungsten-supplemented diet, BBB integrity was protected during reperfusion without inhibition of postischemic hyperemia. This study suggests that early disruption of the BBB to large molecules is mediated by free oxygen radicals, which inhibit rather than cause postischemic hyperemia.
在局灶性脑缺血-再灌注兔模型中，评估了游离氧自由基在血脑屏障（BBB）破坏和缺血后充血中的作用。六组兔子接受了大脑前动脉、大脑中动脉和颅内颈内动脉的夹闭。在这些动脉闭塞1小时前、期间和之后15分钟，使用放射性微球测量脑血流量（CBF）。缺血50分钟后，第1组动物（对照组）接受安慰剂。第2-4组动物接受三种药物之一：10mg/kg过氧化氢酶、5mg/kg甲巯咪唑或10mg/kg吲哚美辛。第五组在诱导缺血前14天接受补充钨的饮食，第六组进行假手术。通过伊文思蓝（EB）-白蛋白染料是否穿过血脑屏障泄漏来确定脑内微血管的完整性，并通过显微分光荧光测定法进行测量。在对照组缺血期间，脑血流量分别降至缺血前水平的14%、7%和11%，分别位于脑的前部、中部和后部，其特征是大量EB-白蛋白染料通过血脑屏障泄漏到缺血半球。在早期再灌注期间，缺血后充血与脑的前部、中部和后部的脑血流量分别增加128%、123%和129%有关。在所有治疗组和接受补充钨饮食的组中，血脑屏障的完整性在再灌注期间得到保护，而不会抑制缺血后充血。这项研究表明，血脑屏障对大分子的早期破坏是由游离氧自由基介导的，游离氧自由基抑制而非导致缺血后充血。
