Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury
Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury
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DOI：
10.1016/s0006-8993(00)02582-8
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发表时间：
2000-09-01
期刊：
影响因子：
2.9
通讯作者：
Thiemermann, C
中科院分区：
文献类型：
--
作者：
Cuzzocrea, S;McDonald, MC;Thiemermann, C
有证据表明，活性氧自由基的过度产生有助于与短暂性脑缺血相关的脑损伤。本研究探讨了tempol（一种可穿过生物膜的水溶性小分子）对沙土鼠（BCO）双侧颈总动脉闭塞和再灌注引起的脑损伤的影响，Tempol治疗沙鼠（30 mg/kg i. p.，在再灌注前30 min和再灌注开始后1 h和6 h）减少缺血后脑水肿的形成。Tempol还减轻脑缺血和再灌注引起的脑丙二醛（MDA）和海马髓过氧化物酶（MPO）水平的增加。对缺血-再灌注脑海马区的免疫组织化学分析显示硝基酪氨酸（过氧亚硝酸盐生成的指标）和聚（ADP-核糖）合成酶（PARS）（DNA单链断裂后该核酶活化的指标）染色阳性。在用Tempol处理的遭受BCO的沙鼠中，硝基酪氨酸和PARS的染色程度显著降低。Tempol增加了存活率，并减少了由脑缺血和再灌注引起的多动（继发于缺血诱导的神经变性）。用tempol处理沙鼠，也减轻了由缺血和再灌注引起的CAI区锥体层神经元的损失。这是第一个证据，表明膜渗透性自由基清除剂tempol减轻了体内短暂脑缺血引起的脑损伤。(C)2000 Elsevier Science B. V.保留所有权利。
There is evidence that the excessive generation of reactive-oxygen radicals contributes to the brain injury associated with transient, cerebral ischemia. This study investigates the effects of tempol, a small, water-soluble molecule, that crosses biological membranes, on the brain injury caused by bilateral occlusion and reperfusion of both common carotid arteries in the gerbil (BCO), Treatment of gerbils with tempol (30 mg/kg i.p. at 30 min prior to reperfusion and at 1 and 6 h after the onset of reperfusion) reduced the formation of post-ischemic brain oedema. Tempol also attenuated the increase in the cerebral levels of malondialdehyde (MDA) and the hippocampal levels of myeloperoxidase (MPO) caused by cerebral ischemia and reperfusion. The immunohistochemical analysis of the hippocampal region of brains subjected to ischemia-reperfusion exhibited positive staining for nitrotyrosine (an indicator of the generation of peroxynitrite) and poly(ADP-ribose) synthetase (PARS) (an indicator of the activation of this nuclear enzyme secondary to single strand breaks in DNA). in gerbils subjected to BCO, which were treated with tempol, the degree of staining fur nitrotyrosine and PARS was markedly reduced. Tempol increased survival and reduced the hyperactivity (secondary to the ischemia-induced neurodegeneration) caused by cerebral ischemia and reperfusion. The loss of neurons from the pyramidal layer of the CAI region caused by ischemia and reperfusion was also attenuated by treatment of gerbils with tempol, This is the first evidence that the membrane-permeable, radical scavenger tempol reduces the cerebral injury caused by transient, cerebral ischemia in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.