Effects of CD11b/18 monoclonal antibody on rats with permanent middle cerebral artery occlusion.

Effects of CD11b/18 monoclonal antibody on rats with permanent middle cerebral artery occlusion.
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发表时间:
1996
期刊:
The American journal of pathology
影响因子:
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通讯作者:
J. Garcìa;K. Liu;M. Bree
J. Garcìa;K. Liu;M. Bree
中科院分区:
其他
文献类型:
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作者:
J. Garcìa;K. Liu;M. Bree

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大脑中动脉永久性闭塞后,从缺血性损伤到梗死的病变进展可能受到白细胞流入缺血性区域的影响。我们旨在评估在动脉闭塞1小时后注射单剂量抗cd11b /18单克隆抗体治疗永久性大脑中动脉闭塞大鼠的有效性。为了模拟缺血性卒中患者的临床情况,在缺血性事件发生后1小时内可以治疗,动脉仍然闭塞。41只成年Wistar大鼠永久性大脑中动脉闭塞,1只进行假手术。1小时后,22只大鼠注射CD11b/18单克隆抗体,另外20只大鼠注射非特异性抗体(n = 10)或缓冲液(n = 10)。动脉闭塞后每隔12 ~ 96小时终止实验。终点包括神经学测试、每日体重评估、外周血白细胞计数、缺血半球苍白面积测量、坏死神经元计数和缺血半球隔离的白细胞计数。在动脉闭塞后12小时终止的实验中(n = 4), CD11b/18单克隆抗体处理组的坏死神经元数量少于对照组(12小时后三个亚组间P值无差异)。注射单克隆抗体CD11b/18后,动脉闭塞动物外周血白细胞计数明显降低(P < 0.05);三组脑缺血半球隔离的白细胞数量无明显差异。三组患者的体重和苍白面积的变化均无显著差异。
The progression of a lesion from ischemic injury to infarct, after the permanent occlusion of a middle cerebral artery, may be influenced by the influx of leukocytes into the ischemic territory. We aimed to evaluate the effectiveness of treating rats that had permanent middle cerebral artery occlusion with a single dose of an anti-CD11b/18 monoclonal antibody injected 1 hour after the arterial occlusion. To mimic the clinical situation of patients with ischemic strokes who may be treated within 1 hour of the ischemic event, the artery remained occluded. Forty-one adult Wistar rats had permanent middle cerebral artery occlusion, and one was subjected to a sham operation. One hour later, 22 rats received CD11b/18 monoclonal antibody and an additional 20 were injected either with a nonspecific antibody (n = 10) or a buffer solution (n = 10). Experiments were terminated at intervals ranging 12 to 96 hours after the arterial occlusion. Endpoints included neurological testing, daily evaluation of body weight, counts of white blood cells in the peripheral blood, measurement of the area of pallor in the ischemic hemisphere, counts of necrotic neurons, and counts of leukocytes sequestered in the ischemic hemisphere. In experiments terminated 12 hours after the arterial occlusion (n = 4), there were fewer necrotic neurons in the group treated with the CD11b/18 monoclonal antibody compared with the two controls (P 12 hours later were not different among the three subgroups. White blood cell counts in peripheral blood were lower in animals with arterial occlusion injected with the monoclonal antibody CD11b/18 (P < .05); numbers of leukocytes sequestered in the ischemic hemisphere were not different in the three groups. Neither changes in body weight nor in the volume of the area of pallor were significantly different among the three groups.