title: Targeting mannose-binding lectin confers long-lasting protection with a surprisingly wide therapeutic window in cerebral ischemia.
abstract: BACKGROUND
  The involvement of the complement system in brain injury has been scarcely investigated. Here, we document the pivotal role of mannose-binding lectin (MBL), one of the recognition molecules of the lectin complement pathway, in brain ischemic injury.
  
  
  RESULTS
  Focal cerebral ischemia was induced in mice (by permanent or transient middle cerebral artery occlusion) and rats (by 3-vessel occlusion). We first observed that MBL is deposited on ischemic vessels up to 48 hours after injury and that functional MBL/MBL-associated serine protease 2 complexes are increased. Next, we demonstrated that (1) MBL(-/-) mice are protected from both transient and permanent ischemic injury; (2) Polyman2, the newly synthesized mannosylated molecule selected for its binding to MBL, improves neurological deficits and infarct volume when given up to 24 hours after ischemia in mice; (3) anti-MBL-A antibody improves neurological deficits and infarct volume when given up to 18 hours after ischemia, as assessed after 28 days in rats.
  
  
  CONCLUSIONS
  Our data show an important role for MBL in the pathogenesis of brain ischemic injury and provide a strong support to the concept that MBL inhibition may be a relevant therapeutic target in humans, one with a wide therapeutic window of application.
authors.affiliation: Neuroscience Department, University of Milan.
authors.forename: Franca
authors.initials: F
authors.lastname: Orsini
authors.forename: Pia
authors.initials: P
authors.lastname: Villa
authors.forename: Sara
authors.initials: S
authors.lastname: Parrella
authors.forename: Rosalia
authors.initials: R
authors.lastname: Zangari
authors.forename: Elisa R
authors.initials: ER
authors.lastname: Zanier
authors.forename: Raffaella
authors.initials: R
authors.lastname: Gesuete
authors.forename: Matteo
authors.initials: M
authors.lastname: Stravalaci
authors.forename: Stefano
authors.initials: S
authors.lastname: Fumagalli
authors.forename: Roberta
authors.initials: R
authors.lastname: Ottria
authors.forename: José J
authors.initials: JJ
authors.lastname: Reina
authors.forename: Alessandra
authors.initials: A
authors.lastname: Paladini
authors.forename: Edoardo
authors.initials: E
authors.lastname: Micotti
authors.forename: Renato
authors.initials: R
authors.lastname: Ribeiro-Viana
authors.forename: Javier
authors.initials: J
authors.lastname: Rojo
authors.forename: Vasile I
authors.initials: VI
authors.lastname: Pavlov
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Stahl
authors.forename: Anna
authors.initials: A
authors.lastname: Bernardi
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: De Simoni
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001929:Brain Edema / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008351:Mannans / Q000378:metabolism / Q000494:pharmacology; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000911:Antibodies, Monoclonal; D008351:Mannans; D037601:Mannose-Binding Lectin; C069858:mannose binding protein A; C097323:polymannose