P-selectin antibody reduces hemorrhage and infarct volume resulting from MCA occlusion in the rat.
We investigated the effect of an anti-P-selectin antibody (RMP-1) on ischemic cell damage and hemorrhage after transient middle cerebral artery occlusion (MCAo) in the rat. Animals were divided into four groups: (1) antibody (Ab) 1 group (n = 14) RMP-1 (2 mg/kg) was administered to rats 1 h prior to induction of 2 h of MCA occlusion; (2) control-vehicle group Ab2 (n = 12) rats were subjected to the same experimental protocol, except that an isotype-matched control antibody was administered; (3) Abl group (n = 10) rats were subjected to 2 h of MCA occlusion and RMP-1 (2 mg/kg) was administered upon reperfusion; (4) control-vehicle group Ab2 (n = 10) rats were subjected to the same experimental protocol, except that an isotype-matched control antibody was administered. Animals were sacrificed 48 h after onset of the MCAo for histological evaluation of infarction and hemorrhage, and to quantify number of neutrophils. The lesion volume was significantly smaller only in pretreated rats (RMP-1 group, 18.7+/-3.1%) compared to the vehicle-treated (31.6+/-2.6%) group (P<0.01). Total area of hemorrhage (5.94 x 10(3)+/-2.86 x 10(3) microm2) in the pre MCAo RMP-1 treated group animals was significantly reduced (P<0.02) compared to the vehicle group (6.1 x 10(4)+/-3.42 x 10(4) microm2), respectively. Our data demonstrate that administration of the anti-P-selectin antibody before transient focal cerebral ischemia in rat brain reduces ischemic cell damage and petechial hemorrhage.
Goussev
A V
AV
Henry Ford Health Sciences Center, Department of Neurology, Detroit, MI 48202, USA.
Zhang
Z
Z
Anderson
D C
DC
Chopp
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001157:Arterial Occlusive Diseases / Q000150:complications*; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002536:Cerebral Arteries / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D019007:P-Selectin / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D009195:Peroxidase