Neuroprotective effect of C1-inhibitor following traumatic brain injury in mice

Background The goal of the study was to evaluate the effects of Cl-inhibitor (Cl-INH), an endogenous glycoprotein endowed with multiple anti-inflammatory actions, on cognitive and histological outcome following controlled cortical impact (CCl) brain injury. Methods Male C57Bl/6 mice (n=48) were Subjected to CCl brain Injury. After brain injury, animals randomly received ail intravenous infusion of either Cl-INH (15 U either at 10 minutes or 1 hour postinjury) or saline (equal volume, 150 mu l at 10 min postinjury). Uninjured control mice received identical surgery and saline injection without brain injury. Cognitive function was evaluated at 4 weeks postinjury using the Morris Water Maze. Mice were subsequently sacrificed, the brains were frozen and serial sections were cut. Traumatic brain lesion was assessed by dividing the area of the ipsilateral hemisphere for the area of the contralateral one at the level Of the injured area of the brain. Findings Brain-injured mice receiving Cl-INH at 10 min postinjury showed attenuated cognitive dysfunction compared to brain-injured mice receiving saline (p<0.01). These mice also showed a significantly reduced traumatic brain lesion compared to mice receiving saline (p<0.01). Mice receiving Cl-INH at 1 hour post injury did not show a significant improvement in either cognitive or histological Outcome. Conclusions Our results suggest that administration of Cl-INH at 10 minutes postinjury attenuates cognitive deficits and histological damage associated with traumatic brain injury.