Pharmacological inhibition of mannose-binding lectin ameliorates neurobehavioral dysfunction following experimental traumatic brain injury

Daiana De Blasio, Stefano Fumagalli, Luca Longhi, Franca Orsini, Alessandro Palmioli, Matteo Stravalaci, Gloria Vegliante, Elisa R. Zanier, Anna Bernardi, Marco Gobbi, Maria Grazia De Simoni

Research output: Contribution to journalArticlepeer-review

Abstract

Mannose-binding lectin is present in the contusion area of traumatic brain-injured patients and in that of traumatic brain-injured mice, where mannose-binding lectin-C exceeds mannose-binding lectin-A. The reduced susceptibility to traumatic brain injury of mannose-binding lectin double knock-out mice (mannose-binding lectin â '/â ') when compared to wild type mice suggests that mannose-binding lectin may be a therapeutic target following traumatic brain injury. Here, we evaluated the effects of a multivalent glycomimetic mannose-binding lectin ligand, Polyman9, following traumatic brain injury in mice. In vitro surface plasmon resonance assay indicated that Polyman9 dose-dependently inhibits the binding to immobilized mannose residues of plasma mannose-binding lectin-C selectively over that of mannose-binding lectin-A. Male C57Bl/6 mice underwent sham/controlled cortical impact traumatic brain injury and intravenous treatment with Polyman9/saline. Ex-vivo surface plasmon resonance studies confirmed that Polyman9 effectively reduces the binding of plasma mannose-binding lectin-C to immobilized mannose residues. In vivo studies up to four weeks post injury, showed that Polyman9 induces significant improvement in sensorimotor deficits (by neuroscore and beam walk), promotes neurogenesis (73% increase in doublecortin immunoreactivity), and astrogliosis (28% increase in glial fibrillary acid protein). Polyman9 administration in brain-injured mannose-binding lectin â '/â ' mice had no effect on post-Traumatic brain-injured functional deficits, suggestive of the specificity of its neuroprotective effects. The neurobehavioral efficacy of Polyman9 implicates mannose-binding lectin-C as a novel therapeutic target for traumatic brain injury.
Original languageItalian
Pages (from-to)938-950
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

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