Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury

Abstract The complement system is believed to contribute to inflammation in acute brain injury. This work defines the neurobehavioral response to traumatic brain injury (TBI) modeled by controlled cortical impact in wild-type mice and in mice carrying gene-targeted deficiencies of individual components of the lectin pathway of complement activation to identify the key components contributing to pathology. Targeted gene deletions include: the recognition subcomponents ficolin-A, CL-11, MBL-C and MBL-A, both individually and combined, and the serine proteases MASP-1, MASP-2 and MASP-3. Our results demonstrate that MASP-2 deficiency brings the highest protective phenotype, countering long-term neuroinflammatory injury following TBI, as shown by reduced neuronal deficits and neuronal cell loss compared to wild-type mice. This study highlights MASP-2 as a promising pharmacological target in patients suffering from TBI, a leading cause of death and disability.