title: Chondroitinase treatment following spinal contusion injury increases migration of oligodendrocyte progenitor cells.
abstract: Following spinal cord injury (SCI), the demyelination of spared intact axons near the lesion site likely contributes to the loss of motor function. This demyelination occurs when oligodendrocytes, the myelinating cells of the central nervous system (CNS), are either destroyed during the initial trauma or die as a result of secondary pathology. In an attempt to remyelinate the affected axons, endogenous oligodendrocyte progenitor cells (OPCs) begin to accumulate at the border of demyelination. However, the differentiation of OPCs into fully myelinating cells is limited. While the reasons for this are unknown, it is well known that the injured spinal cord is rich in inhibitory molecules that block repair. One such family of molecules is the chondroitin sulfate proteoglycans (CSPGs), which are known to be highly inhibitory to the process of axonal elongation. Recent in vitro findings have demonstrated that CSPGs are also highly inhibitory to OPCs, affecting both their migration and differentiation. Treatment with the enzyme chondroitinase ABC (cABC), which removes the glycosaminoglycan side chains of CSPGs, reverses the inhibitory effects of CSPGs on these cells. In the present study, we examined the effects of cABC on the migratory behavior of endogenous OPCs in vivo following a moderate spinal contusion injury. The total number of OPCs surrounding the lesion site was significantly increased after cABC treatment as compared to controls. cABC treatment also enhanced axonal sprouting, but OPC migration occurs along a different time course and appears independent of new process outgrowth. These data suggest that CSPGs in the post-injury environment inhibit the migration of OPCs, as well as axonal regeneration. Therefore, cABC treatment may not only enhance regenerative axonal sprouting, but may also enhance remyelination after SCI.
authors: Department of Cell and Developmental Biology, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
authors: Justin R
authors: JR
authors: Siebert
authors: Dennis J
authors: DJ
authors: Stelzner
authors: Donna J
authors: DJ
authors: Osterhout