Human brain trauma severity is associated with lectin complement pathway activation

Daiana De Blasio, Stefano Fumagalli, Franca Orsini, Laura Neglia, Carlo Perego, Fabrizio Ortolano, Elisa R Zanier, Edoardo Picetti, Marco Locatelli, Nino Stocchetti, Luca Longhi, Peter Garred, Maria-Grazia De Simoni

Research output: Contribution to journalArticlepeer-review


We explored the involvement of the lectin pathway of complement in post-traumatic brain injury (TBI) pathophysiology in humans. Brain samples were obtained from 28 patients who had undergone therapeutic contusion removal, within 12 h (early) or from >12 h until five days (late) from injury, and from five non-TBI patients. Imaging analysis indicated that lectin pathway initiator molecules (MBL, ficolin-1, ficolin-2 and ficolin-3), the key enzymes MASP-2 and MASP-3, and the downstream complement components (C3 fragments and TCC) were present inside and outside brain vessels in all contusions. Only ficolin-1 was found in the parenchyma of non-TBI tissues. Immunoassays in brain homogenates showed that MBL, ficolin-2 and ficolin-3 increased in TBI compared to non-TBI (2.0, 2.2 and 6.0-times) samples. MASP-2 increased with subarachnoid hemorrhage and abnormal pupil reactivity, two indicators of structural and functional damage. C3 fragments and TCC increased, respectively, by 3.5 - and 4.0-fold in TBI compared to non-TBI tissue and significantly correlated with MBL, ficolin-2, ficolin-3, MASP-2 and MASP-3 levels in the homogenates. In conclusion, we show for the first time the direct presence of lectin pathway components in human cerebral contusions and their association with injury severity, suggesting a central role for the lectin pathway in the post-traumatic pathophysiology of human TBI.

Original languageEnglish
Pages (from-to)794-807
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number5
Publication statusPublished - May 2019


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