Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats
Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats
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DOI：
10.1161/01.str.28.5.1060
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发表时间：
1997-05-01
期刊：
影响因子：
8.3
通讯作者：
Fisher, M
中科院分区：
文献类型：
--
作者：
Onal, MZ;Li, FH;Fisher, M
背景与目的胞磷胆碱是一种天然的磷脂酰胆碱前体，具有神经保护作用，目前正在进行临床试验。为了评价延长胞二磷胆碱治疗和早期N-甲基-D-天冬氨酸(NMDA)拮抗剂治疗的潜在协同神经保护作用，在短暂性局灶性脑缺血大鼠模型上测试了胞二磷胆碱和MK-801次优治疗方案的单独和联合治疗。方法4组SD大鼠(每组12只)用线栓法造成大脑中动脉暂时闭塞(MCAO)90min。实验动物随机、盲法分为4组：(1)生理盐水对照组；(2)MCAO后60min静脉推注MK-801 0.5 mg/kg，然后静脉注射生理盐水1mL/kg，连续7d；(3)MCAO后60min静脉注射生理盐水，然后每日静注胞磷胆碱250 mg/kg，连续7d；(4)MK-801+胞磷胆碱(每日1次，连续7d)。用氯化三苯基四氮唑染色评估死后脑梗塞体积。结果第1、3、4天早产儿死亡率分别为33.3%、41.7%、25.0%。平均校正脑梗塞体积第1、2、3组分别为175.2+/-89.3 mm(3)、179.1+/-78.5 mm(3)、163.9+/-73.7 mm(3)、4组为84.7+/-56.8 mm(3)，差异有统计学意义(P
Background and Purpose Citicoline, a naturally occurring precursor of phosphatidylcholine, is neuroprotective and is currently being assessed in clinical trials. To evaluate potential synergistic neuroprotective effects of prolonged citicoline treatment and early N-methyl-D-aspartate (NMDA) antagonist therapy, suboptimal treatment regimens of citicoline and MK-801 were tested alone and in combination in a rat model of temporary focal ischemia.Methods Four groups of Sprague-Dawley rats (n=12 per group) underwent 90 minutes of temporary middle cerebral artery occlusion (MCAO) with the suture model. Animals were randomly and blindly assigned to one of four treatment groups: (1) saline, vehicle; (2) MK-801, 0.5 mg/kg IV bolus at 60 minutes after MCAO followed by saline 1 mL/kg IP daily for 7 days; (3) saline IV at 60 minutes after MCAO followed by citicoline 250 mg/kg IP daily for 7 days; or (4) both MK-801 and citicoline (daily for 7 days) active treatment. Triphenyltetrazolium chloride staining was used to assess postmortem infarct volume. Neurological scores were determined daily.Results Premature mortality between days 2 and 4 was 33.3% in group 1, 41.7% in groups 2 and 3, and 25.0% in group 4. Mean corrected infarct volume was significantly reduced in group 4 compared with the others (175.2+/-89.3 mm(3) in group 1, 179.1+/-78.5 mm(3) in group 2, 163.9+/-73.7 mm(3) in group 3, and 84.7+/-56.8 mm(3) in group 4 [P