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 microl 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.

C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice / L.G. Longhi, C. Perego, F. Ortolano, E.R. Zanier, P. Bianchi, N. Stocchetti, T.K. McIntosh, M.G. De Simoni. - In: CRITICAL CARE MEDICINE. - ISSN 0090-3493. - 37:2(2009 Feb), pp. 659-665.

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

L.G. Longhi;F. Ortolano;N. Stocchetti;
2009-02

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 microl 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.
Complement; Inflammation; Neuroprotection; Traumatic brain injury
Settore MED/41 - Anestesiologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/70327
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