Garcia J H, Liu K F, Bree M P
Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Am J Pathol. 1996 Jan;148(1):241-8.
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 < .05), but this difference was not reflected in the neurological scores. Numbers of necrotic neurons in experiments terminated > 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.
大脑中动脉永久性闭塞后,病变从缺血性损伤发展为梗死的过程,可能会受到白细胞流入缺血区域的影响。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。为模拟可能在缺血事件1小时内接受治疗的缺血性中风患者的临床情况,动脉保持闭塞状态。41只成年Wistar大鼠接受永久性大脑中动脉闭塞,1只进行假手术。1小时后,22只大鼠接受CD11b/18单克隆抗体,另外20只大鼠注射非特异性抗体(n = 10)或缓冲溶液(n = 10)。在动脉闭塞后12至96小时的不同时间点终止实验。终点指标包括神经功能测试、每日体重评估、外周血白细胞计数、缺血半球苍白区面积测量、坏死神经元计数以及缺血半球中滞留的白细胞计数。在动脉闭塞后12小时终止的实验(n = 4)中,与两个对照组相比,接受CD11b/18单克隆抗体治疗的组中坏死神经元较少(P <.05),但这种差异未反映在神经功能评分中。在12小时后终止的实验中,三个亚组之间坏死神经元的数量没有差异。注射单克隆抗体CD11b/18的动脉闭塞动物外周血白细胞计数较低(P <.05);三组中缺血半球中滞留的白细胞数量没有差异。三组之间体重变化和苍白区体积均无显著差异。