Research & Publications
The inability of CNS axons to regenerate and reinnnervate appropriate targets after trauma results in chronic compromise of function that presents a devastating prognosis for TBI, MS, stroke and SCI patients. Numerous studies have identified two broad classes of axon growth inhibitor (AGI) proteins responsible for axon growth arrest, the myelin associated inhibitors (Nogo, MAG, OMgp) and the Chondroitin Sulfate Proteoglycans (CSPGs). Experimental paradigms that negate the activity of these inhibitors in vivo have shown a slight increase in regeneration of damaged axons, but a more dramatic restitution of function. An alternative hypothesis to long-distance axon regeneration-mediated restitution of function would be the reorganization of intact spinal circuitry that often remains after SCI. One of the central goals of my laboratory is to comprehensively evaluate the potential for intact spinal circuits to replace lost connections after SCI, and furthermore define whether negating the action of AGIs supports adaptive or maladaptive axonal reorganization. Complex wiring of the myriad phenotypes of ascending, descending and intrinsic spinal tracts points to tract-specific sensitivity to AGI’s. Understanding the molecular mechanisms that underlie the ability of intact axons to initiate a growth response to adjacent trauma is crucial to the design of therapeutic agents that can either enhance or arrest this response depending on need. Exploiting the plastic potential of intact spinal circuits will offer additional therapeutic tools to encourage restitution of function after CNS injury. In summary, my laboratory is currently utilizing anatomical, electrophysiological, genetic and in vivo imaging methodology to define the extent of plasticity within intact spinal circuitry to investigate the capacity of de novo circuits to restore function after spinal cord injury and therefore reduce the burden of this neurological disease borne by every age group, by every segment of society, by people all over the world.
Brain Diseases; Demyelinating Diseases; Pain; Spinal Cord Injuries; Neurodegenerative Diseases