Correlation between putative inhibitory molecules at the dorsal root entryzone and failure of dorsal root axonal regeneration

The molecular mechanisms involved in preventing regenerating dorsal root ax ons from entering the spinal cord at the dorsal root entry zone (DREZ) are obscure. We used immunohistochemistry, in situ hybridization, and electron microscopy to study axonal regeneration after dorsal rhizotomy in adult rat s and its relationship to cellular changes and the distribution of putative growth inhibitory molecules in this region. Astrocyte processes, ending as bulb-shaped expansions, grew up to 700 mum into the basal lamina tubes of injured roots, where regenerating axons were also present. Some of these ax ons approached or reached the DREZ but grew no further; others turned back toward the ganglion, suggesting the presence of repulsive cues in or near t he DREZ. Tenascin-C mRNA and protein and CSPG stub immunoreactivity were st rongly upregulated in the roots after rhizotomy, but were only weakly expre ssed in the DREZ. Tenascin-R immunoreactivity was confined to CNS tissue, a nd unaffected by rhizotomy. Large, rounded GFAP-negative, NG2-immunoreactiv e cells, a few of which were OX42 positive, were found in the DREZ followin g rhizotomy. Astrocyte processes projecting into the roots were tenascin-R and NG2 negative. Hence, only NG2-expressing cells and tenascin-R were appr opriately situated to inhibit regeneration through the DREZ.