The role of chondroitinase as an adjuvant to peripheral nerve repair.

ABSTRACT

Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of neural regeneration in the peripheral nervous system. Following nerve injury, inhibitory CSPGs accumulate within the endoneurium and Schwann cell basal lamina of the distal nerve stump. The utilization of chondroitinase ABC (chABC) has led to a marked increase in the ability of injured axons to regenerate across gaps through the CSPG-laden extracellular matrix. Experimental models have repeatedly shown chABC to be capable of degrading the CSPGs that hinder neurite outgrowth. In this article, the characterization of CSPGs, their upregulation following peripheral nerve injury, and potential mechanisms behind their growth and inhibition are described. To date, the literature supports that the adjunct use of chABC may be beneficial to peripheral nerve repair in digesting inhibitory CSPGs. chABC has also shown some indication of synergism with other therapies, such as stem cell transplantation. Evidence supporting the use of chondroitinase as a treatment modality in nerve repair, either alone or in combination with other agents, is reviewed within. Finally, several shortcomings of chABC are addressed, notably its thermal stability and physiologic longevity - both hindering its widespread clinical adoption. Future studies are warranted in order to optimize the therapeutic benefits of the chondroitinase enzyme.