POSTISCHEMIC ADMINISTRATION OF AN ANTI-MAC-1 ANTIBODY REDUCES ISCHEMIC CELL-DAMAGE AFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Background and Purpose Postischemic cerebral inflammation may contribute to ischemic cell damage. The CD11b/18 (Mac-1) integrin mediates stimulated neutrophil binding to endothelia. We therefore investigated the effect of administration of an anti-Mac-1 monoclonal antibody on cerebral ischemic cell damage in the rat. Methods Rats (n = 10) were subjected to 2 hours of middle cerebral artery occlusion; the anti-Mac-1 antibody was administered at a dose of 2 mg/kg IV at 1 hour of reperfusion and 1 mg/kg IV at 22 hours of reperfusion or an isotype-matched control antibody (n = 10) was administered using the same experimental protocol. Rats were killed at 46 hours of reperfusion, and brain sections were stained with hematoxylin and eosin for histological evaluation. In a separate population of rats given either vehicle (n = 8) or anti-Mac-1 antibodies (n = 9), intraparenchymal neutrophils were measured by means of a myeloperoxidase assay. Results The lesion volume was significantly smaller (28%) in the anti-Mac-1 antibody group compared with the vehicle control group (P<.01). Numbers of intraparenchymal polymorphonuclear cells were significantly reduced (P<.05) in the cortex of the anti-Mac-1 antibody group compared with the vehicle control group. Conclusions Our data demonstrate that administration of anti-Mac-1 antibody 1 hour after onset of reperfusion results in significant reductions of ischemic cell damage and intraparenchymal neutrophils after transient (2-hour) focal cerebral ischemia in the rat.