Neuroprotective effect of SolCD39, a novel platelet aggregation inhibitor, on transient middle cerebral artery occlusion in rats
Neuroprotective effect of SolCD39, a novel platelet aggregation inhibitor, on transient middle cerebral artery occlusion in rats
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DOI：
10.1161/01.str.0000056169.45365.15
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发表时间：
2003-03-01
期刊：
影响因子：
8.3
通讯作者：
Ginsberg, MD
中科院分区：
文献类型：
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作者：
Belayev, L;Khoutorova, L;Ginsberg, MD
背景和目的-SolCD 39是重组人胞外ATP/腺苷三磷酸酶（NTPDase 1）的可溶形式，代表了一类新的抗血栓药物。SolCD 39阻断并逆转血小板活化，防止额外的血小板募集到生长的血栓中。本研究的目的是检查solCD 39对神经功能缺损，梗死面积和水肿程度的影响后，短暂的大脑中动脉闭塞（MCAO）在rats.Methods-Physiologically控制的Sprague-Dawley大鼠进行了2小时的MCAO逆行插入的腔内缝合线涂聚-L-赖氨酸。在MCAO之前或在1小时或3小时再循环时静脉内施用药剂（solCD 39）。其他组在1小时再循环时接受溶媒（Tris缓冲盐水）或人血白蛋白（作为“阳性”神经保护对照;体重的25%，0.5%）。在闭塞期间（60分钟）和MCAO后3天每天评价神经系统状态。72小时时脑被灌注固定，并测定梗死体积和脑肿胀。结果-与载体组相比，用solCD 39预处理在72小时时显著改善了神经学评分（分别为4.4+/-0.6和7.6+/-0.6; P=0.008）。通过用solCD 39预处理，皮质梗塞面积在多个水平上显著减少。与媒介物相比，通过solCD 39预处理（平均减少48%）和在3小时再循环时solCD 39处理（平均减少51%），总纹状体梗塞面积也显著减少。与媒介物相比，当在缺血之前或在再循环3小时时施用时，用SolCD 39处理显著减少总梗塞体积（针对脑肿胀校正）平均71%至72%。白蛋白治疗显着降低神经评分和总，皮质，皮质下梗死在多个levels，as expected.Conclusions-Treatment与SolCD 39，管理之前或3小时后MCAO，改善神经评分和减少梗死面积相比，车辆。这种类型的药物似乎具有治疗局灶性缺血性卒中的潜力。
Background and Purpose-SolCD39 is a soluble form of recombinant human ecto-ATP/ADPase (NTPDase1) and represents a new class of antithrombotic agents. SolCD39 blocks and reverses platelet activation, preventing recruitment of additional platelets into a growing thrombus. The purpose of this study was to examine the effect of solCD39 on neurological deficit, infarct size, and extent of edema after transient middle cerebral artery occlusion (MCAO) in rats.Methods-Physiologically controlled Sprague-Dawley rats underwent 2-hour MCAO by retrograde insertion of an intraluminal suture coated with poly-L-lysine. The agent (solCD39) was administered intravenously before MCAO or at I -hour or 3-hour recirculation. Other groups received vehicle (Tris-buffered saline) or human albumin (as a "positive" neuroprotective control; 25%, 0.5% of body weight) at 1-hour recirculation. Neurological status was evaluated during occlusion (at 60 minutes) and daily for 3 days after MCAO. Brains were perfusion-fixed at 72 hours, and infarct volumes and brain swelling were determined.Results-Pretreatment with solCD39 significantly improved the neurological score at 72 hours compared with the vehicle group (4.4+/-0.6 versus 7.6+/-0.6, respectively; P=0.008). Cortical infarct areas were significantly reduced at multiple levels by pretreatment with solCD39. Total striatal infarct area was also significantly reduced compared with vehicle by both solCD39 pretreatment (48% mean reduction) and solCD39 treatment at 3-hour recirculation (51% mean reduction). Treatment with SolCD39 significantly reduced total infarct volume (corrected for brain swelling) by an average of 71% to 72% when administered either before ischemia or at 3 hours of recirculation compared with vehicle. Treatment with albumin significantly reduced neurological score and total, cortical, and subcortical infarction at multiple levels, as expected.Conclusions-Treatment with SolCD39, administered either before or at 3 hours after MCAO, improves neurological score and reduces infarct size compared with vehicle. A pharmacological agent of this type appears to have potential for the treatment of focal ischemic stroke.