Expression of chondroitin sulfotransferases in the injured spinal cord

Abstract

We demonstrated that chondroitinase ABC infused into the graft-host interface resolved the glial scar and improved prospects of axonal regeneration into the distal host spinal cord. To identify the cellular source(s) of chondroitin sulfates that contribute to the glial scar, we mapped the expression of chondroitin sulfotransferases in relation to reactive cells about a lateral hemisection of the thoracic cord (T8) of adult Sprague Dawley rats. Riboprobes for chondroitin 6-sulfotransferase (C6ST), chondroitin 4-sulfotransferases (C4ST-1 and C4ST-2) and uronyl 2-sulfotransferase (U2ST) were generated according to reported sequences of the respective cDNAs. In the normal cord, mRNAs of C6ST and C4ST-1 were detected in GFAP-positive astrocytes, RIP-positive oligodendrocytes and OX42-positive microglia. In the lesion epicenter, upregulated expresson of C6ST, C4ST-2 and U2ST transcripts were detected in hypertrophic astrocytes; expression of C6ST and C4ST-1 transcripts were also found in activated (ED1-positive) macrophages. The increased signal intensities were detectable as early as 3 days post-lesion and remained so in the 7-d and 14-d post-lesion cord. The differential expression of chondroitin sulfotransferases in various reactive cells are implicated in the production of chondroitin isoforms of proteoglycan deposits in the gliotic matrix about the lesion. (Supported by RGC Grant #7355/00M).