title: Mannose-binding lectin promotes local microvascular thrombosis after transient brain ischemia in mice.
abstract: OBJECTIVE
  Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/reperfusion and influences the course and prognosis of ischemic stroke.
  
  
  METHODS
  Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation.
  
  
  RESULTS
  Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice.
  
  
  CONCLUSIONS
  MBL promotes brain damage and functional impairment after brain ischemia/reperfusion in mice. These effects are secondary to intravascular thrombosis and impaired relative cerebral blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion.
authors.affiliation: From the Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain (X.d.l.R., C.J., A.M.P.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (A.C., C.J., Á.C., A.M.P.); ICFO-Institut de Ciències Fotòniques, Castelldefels, Spain (A.K.K., C.P.V., H.M.V., T.D.); and Functional Stroke Unit, Hospital Clínic, Barcelona, Spain (A.C., Á.C.).
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Rosa
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cervera
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kristoffersen
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Valdés
authors.forename: Hari M
authors.initials: HM
authors.lastname: Varma
authors.forename: Carles
authors.initials: C
authors.lastname: Justicia
authors.forename: Turgut
authors.initials: T
authors.lastname: Durduran
authors.forename: Ángel
authors.initials: Á
authors.lastname: Chamorro
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage; D001120:Arginine / Q000031:analogs & derivatives; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000235:genetics; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000235:genetics; D010875:Pipecolic Acids / Q000008:administration & dosage; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D013449:Sulfonamides; D013927:Thrombosis / Q000209:etiology* / Q000235:genetics
chemical_list: D000991:Antithrombins; D037601:Mannose-Binding Lectin; D010875:Pipecolic Acids; D013449:Sulfonamides; D005340:Fibrinogen; D001120:Arginine; C031942:argatroban
keywords: brain; complement pathway, mannose-binding lectin; complement system proteins; infarction, middle cerebral artery; reperfusion