Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion
Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion
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DOI：
10.1097/00001756-200008210-00014
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发表时间：
2000-08-21
期刊：
影响因子：
1.7
通讯作者：
Tranmer, BI
中科院分区：
文献类型：
--
作者：
Kimelberg, HK;Feustel, PJ;Tranmer, BI
细胞肿胀激活阴离子通道的抑制剂，包括抗雌激素化合物他莫昔芬（TAM），已被证明可以减弱缺血期间兴奋性氨基酸（EAA）的增加。由于TAM进入中枢神经系统，我们测试了它是否提供保护，免受损害，由于可逆性大脑中动脉闭塞（rMCAo）大鼠。TAM（5 mg/kg，i.v.）在缺血前25分钟输注，有效地将梗死的总体积从328 +/- 34 mm（3）减少到41 +/- 21 mm（3），减少了87%，如TTC染色所测量的。当在再灌注后1小时开始输注时，即在开始rMCAo后3小时输注时，其同样有效。在组织学上也发现了神经元的保护作用。TAM对氢清除率测定的CBF无影响。这似乎是第一次报告的一个显着的神经保护作用的TAM。需要进一步的研究来确定其作用是否是由于抑制EAA释放和/或其他潜在的神经保护作用部位。(C)2000年利平科特威廉姆斯&威尔金斯。
Inhibitors of cell-swelling-activated anion channels, including the antiestrogenic compound tamoxifen (TAM), have been shown to attenuate the increase in excitatory amino acids (EAA) during ischemia. Since TAM enters the CNS we tested whether it provides protection from damage due to reversible middle cerebral artery occlusion (rMCAo) in rats. TAM (5 mg/kg, i.v.) infused 25 min before ischemia, potently reduced the total volume of the infarct from 328 +/- 34 mm(3) to 41 +/- 21 mm(3), a reduction of 87%, as measured by TTC staining. It was equally effective when infused starting at 1 h after reperfusion, i.e. 3 h after initiation of rMCAo. Protection of neurons was also found histologically. TAM had no effect on CBF as measured by hydrogen clearance. This appears to be the first report of a marked neuroprotective effect of TAM. Further studies are needed to determine whether its effects are due to inhibition of EAA release and/or other potential neuroprotective sites of action. (C) 2000 Lippincott Williams & Wilkins.