• Luca Longhi, Franca Orsini, Daiana De Blasio, Stefano Fumagalli, Fabrizio Ortolano, Marco Locatelli, Nino Stocchetti, and Maria-Grazia De Simoni.
• 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.
• Crit. Care Med. 2014 Aug 1;42(8):1910-8.

ObjectiveMannose-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.DesignTranslational research, combining a human/experimental observational study and a prospective experimental study.SettingUniversity hospital/research laboratory.Patients And SubjectsBrain-injured patients, C57Bl/6 mice, and mannose-binding lectin-A and mannose-binding lectin-C double-knockout (-/-) mice.InterventionsUsing 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).Measurements And Main ResultsFollowing 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.ConclusionsMannose-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.

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