A Better Way to Excise Inhibitory Molecules (CSPGs) from a Spinal Cord Injury Scar to Promote Regeneration

A major consequence of spinal cord injury SCI is the development of a glial scar. Although the scar has benefits for tissue repair, it also blocks neural regeneration. Inhibitory chondroitin sulfate proteoglycans CSPGs are elevated in the glial scar and are a major deterrent to successful regeneration. In the present study, we have demonstrated that injured astrocytes produce a wide variety of inhibitory CSPGs. To develop a more efficient method to accomplish CSPG degradation than the bacterial enzyme chondroitinase, we are addressing a normally occurring catabolic protein for CSPG degradation, the neural aggrecanase, ADAMTS-4. We have begun a two-prong approach, employing studies both in vitro, and in vivo. We have produced recombinant ADAMTS-4 protein for experiments in-vitro, or for injection in vivo, alone and in combination with chondroitinase. Thus far, we have focused mainly on the development of critical reagents and methods, and have tested these in proof of principle assays. In parallel, we have begun to develop a reproducible SCI model and are developing behavioral assessments to validate the success of aggrecanase and chondroitinase treatments. The significance of these stages is that they will lead to an efficient means by which to attenuate axonal inhibition, and thereby promote plasticity and regeneration of adult neurons following SCI.