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

doi:10.1177/0271678X18758881

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

Department of Clinical Medicine

16 Citations (Scopus)

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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 language	English
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	39
Issue number	5
Pages (from-to)	794-807
ISSN	0271-678X
DOIs	https://doi.org/10.1177/0271678X18758881
Publication status	Published - 1 May 2019

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De Blasio, D., Fumagalli, S., Orsini, F., Neglia, L., Perego, C., Ortolano, F., Zanier, E. R., Picetti, E., Locatelli, M., Stocchetti, N., Longhi, L., Garred, P., & De Simoni, M. (2019). Human brain trauma severity is associated with lectin complement pathway activation. Journal of Cerebral Blood Flow and Metabolism, 39(5), 794-807. https://doi.org/10.1177/0271678X18758881

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, M 2019, 'Human brain trauma severity is associated with lectin complement pathway activation', Journal of Cerebral Blood Flow and Metabolism, vol. 39, no. 5, pp. 794-807. https://doi.org/10.1177/0271678X18758881

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title = "Human brain trauma severity is associated with lectin complement pathway activation",

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.",

author = "{De Blasio}, Daiana and Stefano Fumagalli and Franca Orsini and Laura Neglia and Carlo Perego and Fabrizio Ortolano and Zanier, {Elisa R} and Edoardo Picetti and Marco Locatelli and Nino Stocchetti and Luca Longhi and Peter Garred and {De Simoni}, Maria-grazia",

year = "2019",

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doi = "10.1177/0271678X18758881",

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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 - 2019/5/1

Y1 - 2019/5/1

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.

U2 - 10.1177/0271678X18758881

DO - 10.1177/0271678X18758881

M3 - Journal article

C2 - 29425056

SN - 0271-678X

VL - 39

SP - 794

EP - 807

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 5

ER -

Human brain trauma severity is associated with lectin complement pathway activation

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