Correlation between Putative Inhibitory Molecules at the Dorsal Root Entry Zone and Failure of Dorsal Root Axonal Regeneration

GM-CSF inhibits glial scar formation and shows long-term protective effect after spinal cord injury

“…CSPGs can actively inhibit neurite outgrowth and neural regeneration after CNS injury as well as function as a physical barrier [35][36][37][38][39]. CSPGs consist of a protein core and covalently coupled glycosaminoglycans (CS-GAGs).…”

Sensory Nerve Regeneration at the CNS-PNS Interface

“…In addition, tenascin-Y, the avian homologue of mammalian tenascin-X, caused rapid collapse of sensory growth cones cultured on fibronectin, and was avoided by growing sensory neurites in microstripe assays (Tucker et al 2001). It is noteworthy, however, that tenascin-C was highly upregulated along injured dorsal roots, where sensory axons regenerate well, whereas it was only weakly expressed at the DREZ (Zhang et al 2001). This observation indicates that tenascin-C is unlikely to be the determining factor for regeneration failure at the DREZ.…”

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

“…Once there, their growth is arrested by the astrocytes of the glia limitans, against which they often form terminal-like axon structures, 77 or from which they turn back, and are redirected peripherally. 78 Based on observations such as these, it has been hypothesized that there exists an astrocytic 'physiological stop signal' at the DREZ which is responsible for the axonal arrest at the DREZ. 79 While the nature of the signal(s) remains unknown, a number of ECM proteins, induced by dorsal rhizotomy, are well-situated to prohibit penetration by sensory axons of CNS tissue, including CSPGs, the CSPG NG2 made by oligodendrocyte precursors, as well as Tenascin-C and Tenascin-R. 78 The astrocytic character of the inhibition strongly suggests secreted factors, and these are most likely to be components of the ECM laid down as a result of astrocyte activation.…”

“…78 Based on observations such as these, it has been hypothesized that there exists an astrocytic 'physiological stop signal' at the DREZ which is responsible for the axonal arrest at the DREZ. 79 While the nature of the signal(s) remains unknown, a number of ECM proteins, induced by dorsal rhizotomy, are well-situated to prohibit penetration by sensory axons of CNS tissue, including CSPGs, the CSPG NG2 made by oligodendrocyte precursors, as well as Tenascin-C and Tenascin-R. 78 The astrocytic character of the inhibition strongly suggests secreted factors, and these are most likely to be components of the ECM laid down as a result of astrocyte activation. A recent DNA microarray carried out in our group to identify rapidly upregulated (3 days post-rhizotomy) astrocytic mRNAs has revealed a large number of candidate stop signals; 80 here we review recent data on a selection of these molecules.…”

“…While more slowly upregulated (only by 6 days post-rhizotomy), chondroitin synthase is likely to also play an important role in glial scar formation since it is involved in CSPG synthesis. 88 The CSPG NG2 has been implicated in regenerative failure, based on its localization in the CNS part of the DREZ; 78 in fact, its upregulation occurs too slowly (after 1 week) to compellingly implicate it in the rapid conversion of the DREZ from permissive to inhibitory (within 3 days) following rhizotomy.…”