Knoblach S M, Faden A I
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
J Neurotrauma. 2002 Sep;19(9):1039-50. doi: 10.1089/089771502760341956.
Intercellular adhesion molecule-1 (ICAM-1) is an endothelial protein that facilitates invasion of leukocytes into the CNS in response to injury or inflammation. ICAM-1 expression correlates with the severity of clinical head injuries, but its importance in secondary injury events is not fully understood. Therefore, we evaluated ICAM-1 expression and the effect of anti-ICAM-1 treatment on motor recovery and neutrophil invasion after traumatic brain injury induced via the lateral fluid-percussion method in the rat. ICAM-1 was expressed in large and small blood vessels within the injured cortex at 10 and 24 h after injury. Repeated administration of anti-ICAM-1 antibody (clone 1A29) at 1, 10, and again at 24 h after injury significantly improved performance in two of three motor tests, compared to saline controls. Equal doses of nonspecific control antibody (IgG) also significantly improved motor test scores, compared to saline controls. Cortical myeloperoxidase activity, an indicator of neutrophil invasion, was significantly reduced 26 h after injury in animals treated with anti-ICAM-1. Animals treated with IgG showed a trend toward reduction that did not reach significance. These data suggest that ICAM-1 may be involved in neutrophil invasion and neurological dysfunction after TBI, but also implicate a role for a nonspecific antibody effect in improved functional outcome.
细胞间黏附分子-1（ICAM-1）是一种内皮蛋白，在损伤或炎症反应时可促进白细胞侵入中枢神经系统。ICAM-1的表达与临床颅脑损伤的严重程度相关，但其在继发性损伤事件中的重要性尚未完全明确。因此，我们通过大鼠侧方液压冲击法诱导创伤性脑损伤后，评估了ICAM-1的表达以及抗ICAM-1治疗对运动恢复和中性粒细胞浸润的影响。损伤后10小时和24小时，ICAM-1在损伤皮质内的大、小血管中表达。与生理盐水对照组相比，在损伤后1小时、10小时及24小时重复给予抗ICAM-1抗体（克隆1A29），在三项运动测试中的两项中显著改善了表现。与生理盐水对照组相比，同等剂量的非特异性对照抗体（IgG）也显著提高了运动测试分数。皮质髓过氧化物酶活性是中性粒细胞浸润的指标，在接受抗ICAM-1治疗的动物损伤后26小时显著降低。接受IgG治疗的动物显示出降低趋势，但未达到显著水平。这些数据表明，ICAM-1可能参与了创伤性脑损伤后的中性粒细胞浸润和神经功能障碍，但也暗示了非特异性抗体效应在改善功能结局中的作用。
