title: C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice.
abstract: OBJECTIVE
  The aim of the study was to evaluate the effects of C1-inhibitor (C1-INH), an endogenous inhibitor of complement and kinin systems, on neurobehavioral and histological outcome following controlled cortical impact brain injury.
  
  
  METHODS
  Experimental prospective randomized study in mice.
  
  
  METHODS
  Experimental laboratory.
  
  
  METHODS
  Male C57Bl/6 mice (n = 81).
  
  
  METHODS
  Mice were subjected to controlled cortical impact brain injury followed by an intravenous bolus of either C1-INH (15 U either at 10 minutes or 1 hour postinjury) or saline (equal volume, 150 microl at 10 minutes postinjury). Sham-operated mice received identical surgery and saline injection without brain injury. Neurological motor function was evaluated weekly for 4 weeks using the Composite Neuroscore. Cognitive function was evaluated at 4 weeks postinjury using the Morris Water Maze. Histological outcome was performed by measuring the contusion volume at 1 week and 4 weeks postinjury.
  
  
  RESULTS
  Brain-injured mice receiving C1-INH at 10 minutes postinjury showed attenuated motor deficits, cognitive dysfunction and reduced contusion volume compared to brain-injured mice receiving saline. Mice receiving C1-INH at 1 hour postinjury showed reduced motor deficits compared to brain-injured mice receiving saline, but no significantly different cognitive and histological outcome. Immunohistochemical analysis showed that 20 minutes after infusion, C1-INH was localised on endothelial cells and in brain tissue surrounding brain capillaries of the injured hemisphere.
  
  
  CONCLUSIONS
  Our results show that post-traumatic administration of C1-INH attenuates neuro-behavioral deficits and histological damage associated with traumatic brain injury.
authors.affiliation: Department of Anesthesia and Critical Care Medicine, Neurosurgical Intensive Care Unit, University of Milano, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Longhi
authors.forename: Carlo
authors.initials: C
authors.lastname: Perego
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ortolano
authors.forename: Elisa R
authors.initials: ER
authors.lastname: Zanier
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianchi
authors.forename: Nino
authors.initials: N
authors.lastname: Stocchetti
authors.forename: Tracy K
authors.initials: TK
authors.lastname: McIntosh
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: De Simoni
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy* / Q000517:prevention & control* / Q000523:psychology; D050718:Complement C1 Inhibitor Protein / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011446:Prospective Studies
chemical_list: D050718:Complement C1 Inhibitor Protein; C487284:Serping1 protein, mouse