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Failure of remyelination is a critical impediment to recovery in multiple sclerosis (MS). Chondroitin sulfate proteoglycans (CSPGs) have been reported to accumulate in MS lesions, and we thus examined the functional roles of CSPGs on oligodendrocyte precursor cells (OPCs), oligodendrocytes, and remyelination.

We evaluated the expression of CSPGs in lysolecithin‐injected mouse spinal cord, an animal model of demyelination and spontaneous remyelination. The functional impact of CSPGs on OPCs and remyelination was investigated using cultured adult murine and human OPCs and by treating demyelinated mice with xyloside to reduce the CSPG deposition that occurred following injury.

Early and robust upregulation of CSPGs following lysolecithin‐induced demyelination was cleared during remyelination. In culture, CSPGs anchored onto the substratum reduced the adhesion …