CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension.
The precise contribution of different CS-GAGs to CSPG-mediated inhibition of axonal growth after CNS injury is unknown. Quantification of the CS-GAGs in uninjured and injured brain (scar tissue) using fluorophore-assisted carbohydrate electrophoresis (FACE) demonstrated that the dominant CS-GAG in the uninjured brain is CS-4 whereas, in glial scar, CS-2, CS-6, and CS-4,6 were over-expressed. To determine if the pattern of sulfation influenced neurite extension, we compared the effects of CS-GAGs with dominant CS-4, CS-6, or CS-4,6 sulfation to intact CSPG (aggrecan), chondroitin (CS-0), and hyaluronan on chick DRG neurite outgrowth. We report that CS-4,6 GAG, one of the upregulated CS-GAGs in astroglial scar, is potently inhibitory and is comparable to intact aggrecan, a CSPG with known inhibitory properties. Thus, a specific CS-GAG that is differentially over-expressed in astroglial scar is a potent inhibitor of neurite extension. These results may influence the design of more specific strategies to enhance CNS regeneration after injury.
Gilbert
Ryan J
RJ
Department of Biomedical Engineering, Biomaterials, Cell and Tissue Engineering Laboratory, Case Western Reserve University, Cleveland, OH 44106-7207, USA.
McKeon
Robert J
RJ
Darr
Aniq
A
Calabro
Anthony
A
Hascall
Vincent C
VC
Bellamkonda
Ravi V
RV
D053674:Aggrecans; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology; D002642:Chick Embryo; D002807:Chondroitin / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002921:Cicatrix / Q000378:metabolism* / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000503:physiopathology; D020439:Growth Cones / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D013431:Sulfates / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
C508321:Acan protein, rat; D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D006131:Growth Inhibitors; D037181:Lectins, C-Type; D011509:Proteoglycans; D013431:Sulfates; C096808:chondroitin 4,6-disulfate; C038142:chondroitin sulfate glycosaminoglycan; D006820:Hyaluronic Acid; D002807:Chondroitin; D002809:Chondroitin Sulfates