title: Mannose-binding lectin is expressed after clinical and experimental traumatic brain injury and its deletion is protective.
abstract: OBJECTIVE
  Mannose-binding lectin protein is the activator of the lectin complement pathway. Goals were (1) to investigate mannose-binding lectin expression after human and experimental traumatic brain injury induced by controlled cortical impact and (2) to evaluate whether mannose-binding lectin deletion is associated with reduced sequelae after controlled cortical impact.
  
  
  METHODS
  Translational research, combining a human/experimental observational study and a prospective experimental study.
  
  
  METHODS
  University hospital/research laboratory.
  
  
  METHODS
  Brain-injured patients, C57Bl/6 mice, and mannose-binding lectin-A and mannose-binding lectin-C double-knockout (-/-) mice.
  
  
  METHODS
  Using anti-human mannose-binding lectin antibody, we evaluated mannose-binding lectin expression in tissue samples from six patients who underwent surgery for a cerebral contusion. Immunohistochemistry was also performed on tissues obtained from mice at 30 minutes; 6, 12, 24, 48, and 96 hours; and 1 week after controlled cortical impact using anti-mouse mannose-binding lectin-A and mannose-binding lectin-C antibodies. We evaluated the effects of mannose-binding lectin deletion in wild-type and mannose-binding lectin-A and mannose-binding lectin-C double-knockout mice. Functional outcome was evaluated using the neuroscore and beam walk tests for 4 weeks postinjury (n = 11). Histological injury was evaluated by comparing neuronal cell counts in the cortex adjacent to the contusion (n = 11).
  
  
  RESULTS
  Following human traumatic brain injury, we observed mannose-binding lectin-positive immunostaining in the injured cortex as early as few hours and up to 5 days postinjury. Similarly in mice, we observed mannose-binding lectin-C-positive immunoreactivity in the injured cortex beginning 30 minutes and persisting up to 1 week postinjury. The extent of mannose-binding lectin-A expression was lower when compared with that of mannose-binding lectin-C. We observed attenuated sensorimotor deficits in mannose-binding lectin (-/-) mice compared with wild-type mice at 2-4 weeks postinjury. Furthermore, we observed reduced cortical cell loss at 5 weeks postinjury in mannose-binding lectin (-/-) mice compared with wild-type mice.
  
  
  CONCLUSIONS
  Mannose-binding lectin expression was documented after traumatic brain injury. The reduced sequelae associated with mannose-binding lectin absence suggest that mannose-binding lectin modulation might be a potential target after traumatic brain injury.
authors.affiliation: 1Department of Pathophysiology and Transplantation, Neurosurgical Intensive Care Unit, University of Milano, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy. 2Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. 3Department of Biomedical Sciences, University of Chieti, Pescara, Italy. 4Department of Neurosurgery, Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Longhi
authors.forename: Franca
authors.initials: F
authors.lastname: Orsini
authors.forename: Daiana
authors.initials: D
authors.lastname: De Blasio
authors.forename: Stefano
authors.initials: S
authors.lastname: Fumagalli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ortolano
authors.forename: Marco
authors.initials: M
authors.lastname: Locatelli
authors.forename: Nino
authors.initials: N
authors.lastname: Stocchetti
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: De Simoni
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D037241:Mannose-Binding Lectins