Effects of Anti-intercellular Adhesion Molecule-1 Antibody on Reperfusion Injury Induced by Late Reperfusion in the Rat Middle Cerebral Artery Occlusion Model

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Abstract
Inflammatory processes have been implicated in the mechanisms of reperfusion injury. The migration of leukocytes into ischemic tissue on reperfusion, which involves binding to the intercellular adhesion molecule (ICAM) of the endothelial cell, is thought to exacerbate tissue injury. The aim of the present study was to assess the effects of an anti-ICAM-1 antibody on reperfusion-induced injury after late reperfusion in a rat middle cerebral artery occlusion (MCAO) suture model. The animals were divided into four groups: 1) Group 1 (n = 7), 6 hours of permanent MCAO; 2) Group 2 (n = 7), 3 hours of MCAO followed by 3 hours of reperfusion; 3) Group 3 (n = 6), 6 hours of permanent MCAO and treatment with anti-ICAM-1 antibody (designated 1A29, 1 mg/kg) at 2 hours after onset of MCAO; and 4) Group 4 (n = 6), 3 hours of MCAO followed by 3 hours of reperfusion and 1A29 treatment. During the experiment, regional cerebral blood flow was measured by a laser Doppler flowmetric scanning technique. At the 6-hour time point, all rats were killed, and the results of leukocyte infiltration by myeloperoxidase activity and histological analysis using 2,3,5-triphenyltetrazolium chloride staining were examined. Regional cerebral blood flow values before and after MCAO were not significantly different among the four groups. Regional cerebral blood flow values after reperfusion were not significantly different in the two reperfused groups. The percentage brain injury volumes in both the total and cortical areas and the myeloperoxidase activity in the latter were significantly larger in Group 2 (the reperfused group) than in the other groups (P < 0.05) but were decreased by anti-ICAM-1 antibody treatment (Group 2 versus Group 4, P < 0.05). However, there were no differences between Groups 1 and 3 without reperfusion. Myeloperoxidase activities correlated positively with infarct volumes (P < 0.01). The findings of this study demonstrate that the anti-ICAM antibody treatment is effective at inhibiting early inflammatory processes and reperfusion-induced injury caused by late arterial recanalization, which would contribute to widening the therapeutic window of thrombolytic therapy.