Chondroitin sulfate proteoglycan immunoreactivity increases following spinal cord injury and transplantation

Extrinsic factors appear to contribute to the lack of regeneration in the i njured adult spinal cord. It is likely that these extrinsic factors include at group of putative growth inhibitory molecules known as chondroitin sulf ate proteoglycans (CSPGs). The aims of this study were to determine: (1) th e consequences of spinal cord contusion injury on CSPG; expression, (2) if CSPGs can be degraded in vivo by exogenous enzyme application, and (3) the effects of intraspinal transplantation on the expression of CSPGs. Chondroi tin 6-sulfate proteoglycan immunoreactivity (CSPG-IR) dramatically increase d following spinal cord contusion injury both at and adjacent to the injury site compared to normal controls (no surgical procedure) and laminectomy-o nly controls by 4 days postinjury. The dramatic increase in CSPG-IR persist ed around the lesion and in the dorsal one-half to two-thirds of the spinal cord for at least 40 days postinjury. Glial fibrillary acidic protein (GFA P)-IR patterns were similarly intensified and spatially restricted as CSPG- IR patterns. These results suggest that: (1) CSPGs may contribute to the la ck of regeneration following spinal cord injury and (2) astrocytes may cont ribute to the production: of CSPGs. In addition, our results show that CSPG s could be cleaved in vivo with exogenous chondroitinase ABC application. T his demonstration of cleavage may the basis for a model to directly assess CSPGs' role in growth inhibition in vivo (studies in progress) and hold pot ential as a therapeutic approach to enhance growth. Interestingly, the robu st, injury-induced CSPG-IR patterns were not altered by intraspinal grafts of fetal spinal cord. The CSPG expression profile in the host spinal cord w as similar to time-matched contusion-only animals. This was also true of GF AP-IR patterns. Furthermore, the fetal spinal cord tissue, which was genera lly CSPG negative at the time of transplantation, developed robust CSPG exp ression by 30 days posttransplantation. This increase in CSPG; expression i n the graft was paired with a moderate increase in GFAP-IR. CSPG-IR pattern s suggest that these molecules may contribute to the limited regeneration s een following intraspinal transplantation. In addition, it suggests that th e growth permissiveness of the graft may change overtime as CSPG expression develops within the graft. These correlations in the injured and transplan ted spinal cord support CSPGs' putative growth inhibitory effect in the adu lt spinal cord. (C) 1999 Academic Press.