TY - JOUR
T1 - C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice
AU - Longhi, Luca
AU - Perego, Carlo
AU - Ortolano, Fabrizio
AU - Zanier, Elisa R.
AU - Bianchi, Paolo
AU - Stocchetti, Nino
AU - McIntosh, Tracy K.
AU - De Simoni, Maria Grazia
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
KW - Complement
KW - Inflammation
KW - Neuroprotection
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=67650398286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650398286&partnerID=8YFLogxK
U2 - 10.1097/CCM.0b013e318195998a
DO - 10.1097/CCM.0b013e318195998a
M3 - Article
C2 - 19114897
AN - SCOPUS:67650398286
VL - 37
SP - 659
EP - 665
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 2
ER -