Effect of mannose binding lectin pharmacological inhibition in controlled impact brain injured mice

Introduction. We have previously shown that mannose binding lectin (MBL), one of the main activators of the lectin complement pathway, is expressed in the injured brain of patients and in that of mice subjected to controlled cortical impact (CCI) and that its deletion (as assessed in MBL-A and -C double KO mice) is protective (Longhi et al. submitted). We have now evaluated the effects of pharmacological MBL inhibition using Polyman-2, a compound that binds MBL-A with high (while MBL-C with low) affinity and endowed with neuroprotective properties (Orsini et al., Circulation 2012). Materials and methods. Eight-week old male C57Bl/6 mice were subjected to anesthesia with Pentobarbital (65 mg/kg) followed by CCI brain injury (parameters: velocity 5 meter/sec and depth 1 mm). At 10 minutes postinjury, mice (n = 8) randomly received an intravenous infusion of either Polyman-2 (142 μg/mouse) or saline (equal volume, 100 μl). Additional mice received identical anesthesia, surgery, and saline/drug to serve as uninjured controls. Neurobehavioral outcome was evaluated weekly for four weeks by performing neuroscore and beam walk test; cognitive function was evaluated at four weeks postinjury using the Morris water maze. Results. All brain-injured mice showed sustained sensorimotor and cognitive deficits. Brain-injured mice receiving saline or Polyman-2 showed similar performance in neuroscore, beam walk and in Morris water maze. Conclusion. Polyman-2 did not improve neurobehavioral performance after TBI. Since post-traumatic expression of MBL-C is greater than that of MBL-A, novel compounds with greater affinity for MBC-C should be investigated in the setting of TBI.