Mannose binding lectin deficiency reduces functional deficits and histological damage after experimental traumatic brain injury

Background: Mannose binding lectin (MBL) is the activator of the lectin complement pathway. After brain ischemia MBL could be a mediator of secondary brain damage, while after brain trauma (TBI) data suggest that it could be linked to neuroprotection. In order to clarify the role of MBL after TBI we characterized its temporal activation and the effects of its inhibition in a model of cerebral contusion. Methods: 1) Male C57/Bl6 (WT) mice received intraperitoneal anesthesia (Pentobarbital, 65 mg/kg) followed by the controlled cortical impact to model TBI (injury parameters: velocity of 5 meter/s and 1 mm depth of deformation). MBL immunostaining was evaluated at 30 min, 6, 12, 24, 48, 96 h and 1 week after TBI using anti MBL-A and MBL-C antibodies. 2) The effects of MBL inhibition were evaluated in WT and MBL double knockout (-/-) mice. Functional outcome was tested using the Neuroscore and Beam Walk test weekly for 4 weeks postinjury. Histologic outcome was evaluated by neuronal cell count in the cortex adjacent to the contusion. Results: We observed MBL-C positive immunostaining in the injured cortex starting at 30 minutes postinjury and up to 1 week, suggestive of an activation of this pathway. MBL-C was observed both at endothelial and tissue level. MBL-A was detected in the injured brain but its staining was much lower compared to that of MBL-C. Injured WT and MBL (-/-) mice showed motor deficits up to 4 weeks postinjury when compared to their controls. Motor deficits were reduced in MBL (-/-) compared to WT mice at 2-4 weeks postinjury (p<0.01 for Neuroscore and Beam Walk). Moreover we observed a reduced cortical cell loss at 4 weeks postinjury in MBL (-/-) mice compared to WT (p < 0.05). Conclusions: We observed that 1) TBI induced MBL deposition/synthesis on injured vessels and in the brain tissue; 2) MBL deficiency was associated with functional neuroprotection, suggesting that MBL modulation might be a potential therapeutic target after TBI.