Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat.
OBJECTIVE
Postischemic cerebral inflammation may contribute to ischemic cell damage. Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on endothelial cells that facilitates leukocyte adhesion. We investigated the effect of administration of an anti-ICAM-1 antibody (1A29) on ischemic cell damage after transient (2-hour) or permanent middle cerebral artery (MCA) occlusion in the Wistar rat.


METHODS
Groups studied were as follows: (1) transient MCA occlusion: rats were subjected to 2 hours of MCA occlusion, and after 1 hour of reperfusion they were treated with 1A29 (n = 11) or an isotype control antibody (n = 9); and (2) permanent MCA occlusion: rats were treated with 1A29 (n = 9) or an isotype control antibody (n = 7) 2 hours after onset of MCA occlusion. All animals were killed 1 week after onset of ischemia. Brain sections were stained with hematoxylin and eosin for histological evaluation.


RESULTS
Significant reductions (P < .05) in both volume (44%) of the ischemic lesion and weight loss were found in animals subjected to transient MCA occlusion and treated with 1A29 compared with vehicle-treated animals. In contrast, in animals subjected to permanent MCA occlusion the lesion and the temporal profile of body weight were not altered by 1A29 administration.


CONCLUSIONS
Ischemic cell damage is promoted by postischemic inflammatory response after 2 hours of transient MCA occlusion, and ischemic cell damage is reduced by administration of an anti-ICAM-1 antibody during reperfusion.
Zhang
R L
RL
Henry Ford Health Sciences Center, Department of Neurology, Detroit, Mich 48202, USA.
Chopp
M
M
Jiang
N
N
Tang
W X
WX
Prostak
J
J
Manning
A M
AM
Anderson
D C
DC
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001772:Blood Cell Count; D001835:Body Weight; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D002536:Cerebral Arteries / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000906:Antibodies; D018799:Intercellular Adhesion Molecule-1