C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice

Luca Longhi, Carlo Perego, Fabrizio Ortolano, Elisa R. Zanier, Paolo Bianchi, Nino Stocchetti, Tracy K. McIntosh, Maria Grazia De Simoni

Research output: Contribution to journalArticle

Abstract

OBJECTIVE:: The aim of the study was to evaluate the effects of C1-inhibitor (C1-INH), an endogenous inhibitor of complement and kinin systems, on neurobehavioral and histological outcome following controlled cortical impact brain injury. DESIGN:: Experimental prospective randomized study in mice. SETTING:: Experimental laboratory. SUBJECTS:: Male C57Bl/6 mice (n = 81). INTERVENTIONS:: Mice were subjected to controlled cortical impact brain injury followed by an intravenous bolus of either C1-INH (15 U either at 10 minutes or 1 hour postinjury) or saline (equal volume, 150 μl at 10 minutes postinjury). Sham-operated mice received identical surgery and saline injection without brain injury. Neurological motor function was evaluated weekly for 4 weeks using the Composite Neuroscore. Cognitive function was evaluated at 4 weeks postinjury using the Morris Water Maze. Histological outcome was performed by measuring the contusion volume at 1 week and 4 weeks postinjury. MEASUREMENTS AND MAIN RESULTS:: Brain-injured mice receiving C1-INH at 10 minutes postinjury showed attenuated motor deficits, cognitive dysfunction and reduced contusion volume compared to brain-injured mice receiving saline. Mice receiving C1-INH at 1 hour postinjury showed reduced motor deficits compared to brain-injured mice receiving saline, but no significantly different cognitive and histological outcome. Immunohistochemical analysis showed that 20 minutes after infusion, C1-INH was localised on endothelial cells and in brain tissue surrounding brain capillaries of the injured hemisphere. CONCLUSION:: Our results show that post-traumatic administration of C1-INH attenuates neuro-behavioral deficits and histological damage associated with traumatic brain injury.

Original languageEnglish
Pages (from-to)659-665
Number of pages7
JournalCritical Care Medicine
Volume37
Issue number2
DOIs
Publication statusPublished - Feb 2009

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Keywords

  • Complement
  • Inflammation
  • Neuroprotection
  • Traumatic brain injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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