Regeneration failure in the adult mammalian CNS is not due to an inability of central neurons to elongate and remyelinate, but rather to the non-permissive nature of the CNS environment. Our studies identified fibrin as a novel inhibitory protein that delays nerve regeneration after sciatic nerve injury and showed that fibrin degradation correlates with nerve regeneration, while decreased proteolytic activity in the nervous tissue exacerbates damage. Fibrin, derived from the blood protein fibrinogen, is deposited in the nervous tissue after injury or disease associated with blood-brain barrier leakage. For example, in Multiple Sclerosis fibrin deposition correlates with demyelination and persists in plaques that do not show signs of repair. Our research, using in vivo models of inflammatory demyelination, focuses on the cellular mechanisms and molecular pathways that fibrin uses to affect remyelination and inflammation in the nervous system in an attempt to develop novel therapeutic strategies for neuroinflammatory diseases.

Our work is supported by the National Multiple Sclerosis Society (NMSS), the Christopher Reeve Foundation, and the National Institutes of Health NIH/NINDS.