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 journalArticle

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.

Original languageEnglish
Pages (from-to)794-807
JournalJournal of Cerebral Blood Flow and Metabolism
Volume39
Issue number5
DOIs
Publication statusPublished - 2019

Fingerprint

Mannose-Binding Lectin Complement Pathway
Complement Activation
Mannose-Binding Protein-Associated Serine Proteases
Brain Injuries
Lectins
Contusions
Brain
Complement C3
Traumatic Brain Injury
ficolin
Wounds and Injuries
Subarachnoid Hemorrhage
Pupil
Immunoassay

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Human brain trauma severity is associated with lectin complement pathway activation. / De Blasio, Daiana; Fumagalli, Stefano; Orsini, Franca; Neglia, Laura; Perego, Carlo; Ortolano, Fabrizio; Zanier, Elisa R.; Picetti, Edoardo; Locatelli, Marco; Stocchetti, Nino; Longhi, Luca; Garred, Peter; De Simoni, Maria Grazia.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 39, No. 5, 2019, p. 794-807.

Research output: Contribution to journalArticle

De Blasio, Daiana ; Fumagalli, Stefano ; Orsini, Franca ; Neglia, Laura ; Perego, Carlo ; Ortolano, Fabrizio ; Zanier, Elisa R. ; Picetti, Edoardo ; Locatelli, Marco ; Stocchetti, Nino ; Longhi, Luca ; Garred, Peter ; De Simoni, Maria Grazia. / Human brain trauma severity is associated with lectin complement pathway activation. In: Journal of Cerebral Blood Flow and Metabolism. 2019 ; Vol. 39, No. 5. pp. 794-807.
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T1 - Human brain trauma severity is associated with lectin complement pathway activation

AU - De Blasio, Daiana

AU - Fumagalli, Stefano

AU - Orsini, Franca

AU - Neglia, Laura

AU - Perego, Carlo

AU - Ortolano, Fabrizio

AU - Zanier, Elisa R.

AU - Picetti, Edoardo

AU - Locatelli, Marco

AU - Stocchetti, Nino

AU - Longhi, Luca

AU - Garred, Peter

AU - De Simoni, Maria Grazia

PY - 2019

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N2 - 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.

AB - 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.

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