Central nervous system demyelination occurs in numerous conditions, including multiple sclerosis (MS). Remyelination in acute lesions involves the recruitment and maturation of oligodendrocyte progenitor cells (OPCs). However, remyelination fails in chronic lesions in part due to the failure of OPCs to mature into myelinating oligodendrocytes (OLs). Digestion products of the glycosaminoglycan hyaluronan (HA), generated by hyaluronidase activity within demyelinating lesions, are among the signals that block OPC maturation and remyelination. However, the identity and source of this hyaluronidase activity is unknown.