EFFECT OF MCI-186 ON BRAIN EDEMA IN RATS
EFFECT OF MCI-186 ON BRAIN EDEMA IN RATS
复制标题
DOI：
10.1161/01.str.20.9.1236
复制
发表时间：
1989-09-01
期刊：
影响因子：
8.3
通讯作者：
ISHIBASHI, A
中科院分区：
文献类型：
--
作者：
NISHI, H;WATANABE, T;ISHIBASHI, A
我们给72只大鼠注射5。浓度为3.0% wt:vol的聚醋酸乙烯酯注入左颈内动脉，在左大脑半球产生永久性栓塞，再现性发生同侧脑水肿。栓塞24小时后通过测定脑水含量和钠、钾浓度评估水肿。在该模型中，自由基清除剂MCI-186在1.0和3.0 mg/kg静脉注射时呈剂量依赖性地预防脑水肿。在3.0 mg/kg静脉滴注MCI-186时，栓塞左半球的水含量显著降低1.5%，钠钾平衡改善至正常范围内。地塞米松1.0 mg/kg静脉滴注对脑水肿有抑制作用，3.0 mg/kg静脉滴注对脑水肿无明显抑制作用。吲哚美辛4.0 mg/kg ig对脑水肿无明显影响。我们认为，从神经元细胞膜磷脂中释放的花生四烯酸的环加氧酶代谢物不太可能参与聚醋酸乙烯诱导的永久性脑水肿的发病机制。我们的研究结果表明，MCI-186通过抑制脂氧合酶代谢物（包括自由基或脂质过氧化物）的产生来减轻脑水肿，并且它可能被证明对脑缺血相关脑水肿的治疗有价值。
We induced brain edema in 72 rats by injecting 5 .mu.l of 3.0% wt:vol polyvinyl acetate into the left internal carotid artery, producing permanent embolization in the left cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 hours after embolization by determining the brain water content and the sodium and potassium concentrations. In this model, the free radical scavenger MCI-186 at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner. At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and improved the sodium-potassium balance to within the normal range in the embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0 mg/kg i.v. did not significantly inhibit the development of brain edema. Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest that the cyclooxygenase metabolites of arachidonic acid liberated from neuronal cell membrane phospholipids are not likely to be involved in the pathogenesis of permanent brain edema induced by polyvinyl acetate. Our results suggest that MCI-186 attenuates brain edema by suppressing the production of lipoxygenase metabolites, including free radicals or lipids peroxides, and that it may prove valuable for the treatment of brain edema associated with cerebral ischemia.