Citation

De Blasio D, Fumagalli S, Orsini F, Neglia L, Perego C, Ortolano F, Zanier ER, Picetti E, Locatelli M, Stocchetti N, Longhi L, Garred P, De Simoni MG. J. Cereb. Blood Flow Metab. 2019; 39(5): 794-807.

Affiliation

IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

Copyright

(Copyright © 2019, Nature Publishing Group)

DOI

10.1177/0271678X18758881

PMID

29425056

Abstract

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.

Language: en

Keywords

MBL-associated serine proteases; Traumatic brain injury; complement system; lectin complement pathway; neuroinflammation