Antibody to the α4 integrin decreases infarct size in transient focal cerebral ischemia in rats
Antibody to the α4 integrin decreases infarct size in transient focal cerebral ischemia in rats
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DOI：
10.1161/01.str.32.1.206
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发表时间：
2001-01-01
期刊：
影响因子：
8.3
通讯作者：
Winn, R
中科院分区：
文献类型：
--
作者：
Becker, K;Kindrick, D;Winn, R
背景和目的-炎症是一个涉及中性粒细胞、淋巴细胞和单核细胞的过程，参与脑缺血性损伤。阻断中性粒细胞与内皮细胞的粘附可改善实验性卒中的预后。方法：雄性刘易斯大鼠大脑中动脉闭塞3小时，然后再灌注45小时，缺血开始后2小时，一组动物接受腹膜内注射α（4）整联蛋白抗体（n=16）;另一组注射同种型对照抗体（n=11）。在卒中后不同时间点评估神经系统检查、体温和体重。动物在缺血发作后48小时处死，以测定梗死体积和白细胞计数。结果在任何时间，体温或体重均无显着差异。在缺血后24小时（2.0+/-1.2对3.0+/-0.4; P=0.006）和48小时（2.0+/-1.2对3.0 +/-0.8; P=0.011），用抗-或-抗体治疗的动物的神经学评分（缺陷）显著较少。抗α 4治疗组动物的外周血白细胞计数显著较高（6.8+/-2.2X10（9）vs. 2.9+/-1.9X10（9）; P=0.001），并显示淋巴细胞/单核细胞占优势（86.0+/-16.2% vs. 71.0+/-15.6%; P=0.008）。用抗α 4抗体治疗的动物，（120.1 ± 51.21对173.7 ± 42.29 mm（3）;结论：这些数据支持淋巴细胞和单核细胞在脑缺血损伤中的作用，并表明即使在缺血发作后阻断α 4，可改善神经功能预后并减少梗死体积。
Background and Purpose-Inflammation, a process that involves neutrophils, lymphocytes, and monocytes, contributes to cerebral ischemic injury. Blockade of neutrophil adhesion to endothelium improves outcome after experimental stroke. In this study we sought to assess the contribution of lymphocytes and monocytes to ischemic brain injury.Methods-Male Lewis rats underwent 3 hours of middle cerebral artery occlusion followed by 45 hours of reperfusion, Two hours after the onset of ischemia, one group of animals received an intraperitoneal injection of antibodies to the alpha (4) integrin (n=16); another group was injected with an isotype control antibody (n=11). Neurological examination, body temperature, and body weight were assessed at different time points after stroke. Animals were killed 48 hours after the onset of ischemia for determination of infarct volume and leukocyte counts.Results-There were no significant differences in body temperature or weight at any time. Neurological scores (deficits) were significantly less in animals treated with anti-or, antibodies at 24 (2.0+/-1.2 versus 3.0+/-0.4; P=0.006) and 48 (2.0+/-1.2 versus 3.0+/-0.8; P=0.011) hours after ischemia. Peripheral blood leukocyte counts were significantly higher in anti-alpha (4)-treated animals (6.8+/-2.2X10(9) versus 2.9+/-1.9X10(9); P=0.001) and revealed a lymphocyte/monocyte predominance (86.0+/-16.2% versus 71.0+/-15.6%; P=0.008). Infarct volume was significantly less in animals treated with antibodies to alpha (4) (120.1+/-51.21 versus 173.7+/-42.29 mm(3); P=0.012).Conclusions-These data support a role for lymphocytes and monocytes in cerebral ischemic injury and show that blockade of alpha (4), even when instituted after the onset of ischemia, can improve neurological outcome and decrease infarct volume.