Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats.
OBJECTIVE
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 i.v. at 1 hour of reperfusion and 1 mg/kg i.v. 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.
Chopp
M
M
Department of Neurology, Henry Ford Hospital, Detroit, Mich. 48202.
Zhang
R L
RL
Chen
H
H
Li
Y
Y
Jiang
N
N
Rusche
J R
JR
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D004906:Erythrocyte Count; D007167:Immunotherapy; D007958:Leukocyte Count; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D016177:Macrophage-1 Antigen