Chondroitin sulphate proteoglycans in the CNS injury response.
As the preceding discussion has demonstrated, experimental data now indicate that the expression of a number of different CSPGs is increased following CNS injury. The hyalectans neurocan, versican and [figure: see text] brevican, plus NG2 and phosphacan are upregulated following injury and all have been shown to exhibit inhibitory effects on neurite outgrowth in vitro. It is likely therefore that the increased expression of these molecules contributes to the non-permissive nature of the glial scar. The relative contributions of individual molecules remain, however, to be determined. It is important to remember also that not only does the glial scar contain many different inhibitory molecules, but that these are the products of a number of different cells, including not just astrocytes, but also oligodendrocyte progenitor and meningeal cells. It is arguable that the latter two cell types make a greater contribution than astrocytes to the inhibitory environment of the injured CNS. Recently, attempts have been made to alter the CSPG component of the glial scar in the hope that this will facilitate improved axonal regeneration. Three studies (Bradbury et al., 2002; Yick et al., 2000; Moon et al., 2001) have reported an improved regenerative response following treatment of the injured CNS with chondroitinase ABC. CSPGs represent a significant source of inhibition within the injured CNS; these studies indicate that successful CNS regeneration may be brought about by interventions which target these molecules and/or the cells which produce them.
Morgenstern
Daniel A
DA
Physiological Laboratory, Centre for Brain Repair, Cambridge University, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK.
Asher
Richard A
RA
Fawcett
James W
JW
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins / Q000502:physiology; D016501:Neurites / Q000502:physiology; D058580:Neurocan; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D058580:Neurocan; C508322:VCAN protein, human; D053675:Versicans; C076817:NCAN protein, human