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 (5.94x10(3)+/-2.86x10(3) mu m(2)) in the pre MCAo RMP-1 treated group animals was significantly reduced (P<0.02) compared to the vehicle group (6.1x10(4)+/-3.42x10(4) mu m(2)), 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. (C) 1998 Published by Elsevier Science B.V. All rights reserved.