Dorsal root injury leads to reactive gliosis and to disintegration of axons and myelin sheaths (Wallerian degeneration) in the dorsal root entry zone (DREZ) and in the spinal cord dorsal column beyond the DREZ, two regions that have distinct growth-inhibitory properties. This disparity could be due to differences in glial cell activation, and/or to differential gene expression. Laser capture microdissection followed by quantitative analysis of mRNA expression by real-time PCR as well as immunohistochemical analysis revealed that glial markers were differentially expressed post-injury. In addition, the number of glial cells undergoing cell division was different, and the proportion of icroglia/
macrophages amongst dividing cells was higher in the dorsal column than the DREZ. Furthermore, transcripts for the chondroitin sulfate proteoglycans Brevican and Versican were found to be preferentially up-regulated in the DREZ and not the dorsal column. These results clearly identify two proteoglycans as potential key molecules participating in the highly inhibitory properties of the DREZ and reveal distinct glial activation in the two regions. They provide the first molecular evidence in support of earlier work indicating that the dorsal column is less inhibitory to sensory axonal growth after injury than the DREZ. Strategies to selectively decrease the expression of these CSPGs by RNA interference could therefore provide novel tools to promote repair following spinal cord or brachial plexus injury. This comparative strategy may allow to discover additional molecules such as cytokines and
chemokines involved in inflammation as potential highly selective targets
for ameliorating axonal regeneration post-injury.