title: Neutrophils contribute to intracerebral haemorrhages after treatment with recombinant tissue plasminogen activator following cerebral ischaemia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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 < 0.05). This depletion was associated with a decrease in cerebral infiltration by neutrophils and a decrease of endothelium-dependent, vascular dysfunction in isolated MCA, induced by the ischaemia/reperfusion and t-PA treatment. Brain infarct volume was significantly decreased after vinblastine treatment (159 +/- 13 mm(3) vs. 243 +/- 16 mm(3) with saline; P < 0.01) but not after depletion with mAbRP3 (221 +/- 22 mm(3)).
  
  
  CONCLUSIONS
  Our results showed that pharmacological depletion of PMNs prevented t-PA-induced ICH, in parallel with a decrease in cerebral infiltration by PMNs and a decreased endothelial dysfunction in cerebral blood vessels.
authors.affiliation: EA1046, Département de Pharmacologie médicale, Institut de Médecine Prédictive et de Recherche Thérapeutique, Université de Lille 2, Faculté de Médecine, Centre Hospitalier Universitaire, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gautier
authors.forename: Thavarak
authors.initials: T
authors.lastname: Ouk
authors.forename: Olivier
authors.initials: O
authors.lastname: Petrault
authors.forename: Jacques
authors.initials: J
authors.lastname: Caron
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000097:blood* / Q000150:complications; D002543:Cerebral Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006973:Hypertension / Q000097:blood* / Q000150:complications; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000166:cytology*; D051381:Rats; D011918:Rats, Inbred SHR; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013927:Thrombosis / Q000097:blood / Q000150:complications; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator