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P-selectin antibody reduces hemorrhage and infarct volume resulting from MCA occlusion in the rat
A V Goussev1, Z Zhang, D C Anderson
1Henry Ford Health Sciences Center, Department of Neurology, Detroit, MI 48202, USA.
Abstract:
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.
Insights
Pretreatment with an anti-P-selectin antibody (RMP-1) significantly reduced ischemic cell damage and hemorrhage in a rat model of middle cerebral artery occlusion (MCAo). This finding highlights the potential therapeutic benefit of anti-P-selectin therapy for acute ischemic stroke.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Ischemic stroke involves cell damage and hemorrhage.
- P-selectin plays a role in inflammatory responses during ischemia.
Purpose of the Study:
- To evaluate the efficacy of an anti-P-selectin antibody (RMP-1) in reducing ischemic cell damage and hemorrhage.
- To investigate the effect of RMP-1 administration timing on outcomes after transient middle cerebral artery occlusion (MCAo).
Main Methods:
- Rats underwent 2-hour MCAo and were treated with RMP-1 or a control antibody before occlusion or upon reperfusion.
- Histological analysis assessed lesion volume, hemorrhage, and neutrophil infiltration 48 hours post-MCAo.
Main Results:
- Pretreatment with RMP-1 significantly reduced lesion volume (18.7% vs. 31.6% in controls, P<0.01).
- RMP-1 pretreatment also significantly decreased hemorrhage area (P<0.02).
- Treatment upon reperfusion did not show significant protective effects.
Conclusions:
- Administration of anti-P-selectin antibody RMP-1 before focal cerebral ischemia in rats mitigates ischemic injury and hemorrhage.
- Targeting P-selectin represents a potential therapeutic strategy for acute ischemic stroke.