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


METHODS
Experimental prospective randomized study in mice.


METHODS
Experimental laboratory.


METHODS
Male C57Bl/6 mice (n = 81).


METHODS
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.


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.


CONCLUSIONS
Our results show that post-traumatic administration of C1-INH attenuates neuro-behavioral deficits and histological damage associated with traumatic brain injury.
Longhi
Luca
L
Department of Anesthesia and Critical Care Medicine, Neurosurgical Intensive Care Unit, University of Milano, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy.
Perego
Carlo
C
Ortolano
Fabrizio
F
Zanier
Elisa R
ER
Bianchi
Paolo
P
Stocchetti
Nino
N
McIntosh
Tracy K
TK
De Simoni
Maria Grazia
MG
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy* / Q000517:prevention & control* / Q000523:psychology; D050718:Complement C1 Inhibitor Protein / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011446:Prospective Studies
D050718:Complement C1 Inhibitor Protein; C487284:Serping1 protein, mouse