Bovine CNS myelin contains neurite growth-inhibitory activity associated with chondroitin sulfate proteoglycans

The absence of fiber regrowth in the injured mammalian CNS is influenced by several different factors and mechanisms. Besides the nonconducive propert ies of the glial scar tissue that forms around the lesion site, individual molecules present in CNS myelin and expressed by oligodendrocytes, such as NI-35/NI-250, bNI-220, and myelin-associated glycoprotein (MAG), have been isolated and shown to inhibit axonal growth. Here, we report an additional neurite growth-inhibitory activity purified from bovine spinal cord myelin that is not related to bNI-220 or MAG. This activity can be ascribed to the presence of two chondroitin sulfate proteoglycans (CSPGs), brevican and th e brain-specific versican V2 splice variant. Neurite outgrowth of neonatal cerebellar granule cells and of dorsal root ganglion neurons in vitro was s trongly inhibited by this myelin fraction enriched in CSPGs. Immunohistoche mical staining revealed that brevican and versican V2 are present on the su rfaces of differentiated oligodendrocytes. We provide evidence that treatme nt of oligodendrocytes with the proteoglycan synthesis inhibitors beta-xylo sides can strongly influence the growth permissiveness of oligodendrocytes. beta-Xylosides abolished cell surface presentation of brevican and versica n V2 and reversed growth cone collapse in encounters with oligodendrocytes as demonstrated by time-lapse video microscopy. Instead, growth cones were able to grow along or even into the processes of oligodendrocytes. Our resu lts strongly suggest that brevican and versican V2 are additional component s of CNS myelin that contribute to its nonpermissive substrate properties f or axonal growth. Expression of these CSPGs on oligodendrocytes may indicat e that they participate in the restriction of structural plasticity and reg eneration in the adult CNS.