Neutrophils contribute to intracerebral haemorrhages after treatment with recombinant tissue plasminogen activator following cerebral ischaemia

Background and purpose:  Polymorphonuclear neutrophils (PMNs) contribute to the vascular damage caused by transient cerebral ischaemia. Here we have evaluated the role of PMNs in intracerebral haemorrhage (ICH) induced in a model of thrombolysis with recombinant tissue plasminogen activator (t‐PA) d...

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Bibliographic Details
Published in:British journal of pharmacology 2009-02, Vol.156 (4), p.673-679
Main Authors: Gautier, Sophie, Ouk, Thavarak, Petrault, Olivier, Caron, Jacques, Bordet, Régis
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain Ischemia - blood
Brain Ischemia - complications
Cerebral Hemorrhage - blood
Cerebral Hemorrhage - chemically induced
haemorrhages
Hypertension - blood
Hypertension - complications
Male
Medical sciences
Neurology
Neutrophil Infiltration - drug effects
neutrophils
Neutrophils - cytology
Pharmacology. Drug treatments
Rats
Rats, Inbred SHR
Recombinant Proteins - adverse effects
Recombinant Proteins - therapeutic use
Research Papers
stroke
Thrombosis - blood
Thrombosis - complications
Tissue Plasminogen Activator - adverse effects
Tissue Plasminogen Activator - therapeutic use
t‐PA
Vascular diseases and vascular malformations of the nervous system
vascular endothelium
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Summary:Background and purpose:  Polymorphonuclear neutrophils (PMNs) contribute to the vascular damage caused by transient cerebral ischaemia. Here we have evaluated the role of PMNs in intracerebral haemorrhage (ICH) induced in a model of thrombolysis with recombinant tissue plasminogen activator (t‐PA) during the acute phase of cerebral ischaemia. Experimental approach:  The middle cerebral artery (MCA) of male spontaneously hypertensive rats was occluded for 1 h followed by reperfusion and, 5 h later, infusion of thrombolytic products (generated in vitro by t‐PA on autologous clots). Effects of pretreatment (before the MCA occlusion) with vinblastine (4 days before; 0.5 mg·kg−1), monoclonal anti‐neutrophil antibody (mAbRP3; 12 h, 0.3 mg·kg−1) or saline on ICH, neutrophil infiltration, MCA vascular reactivity and brain infarct volume were assessed, 24 h after the beginning of reperfusion. Key results:  Depletion of circulating neutrophils significantly reduced t‐PA‐induced ICH (vinblastine, 4.6 ± 1.0; mAbRP3, 5.2 ± 1.0 vs. saline, 10.8 ± 2.7 haemorrhages; P 
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.2009.00068.x