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Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jones, Leonard L. Sajed, Dana Tuszynski, Mark H. |
| Copyright Year | 2003 |
| Abstract | Increased expression of certain extracellular matrix (ECM) molecules after CNS injury is believed to restrict axonal regeneration. The chondroitin sulfate proteoglycans (CSPGs) are one such class of ECM molecules that inhibit neurite outgrowth in vitro and are upregulated after CNS injury. We examined growth responses of several classes of axons to this inhibitory environment in the presence of a cellular fibroblast bridge in a spinal cord lesion site and after a growth factor stimulus at the lesion site (fibroblasts genetically modified to secrete NGF). Immunohistochemical analysis showed dense labeling of the CSPGs NG2, brevican, neurocan, versican, and phosphacan at the host-lesion interface after spinal cord injury (SCI). Furthermore, robust expression of NG2, and to a lesser extent versican, was also observed throughout grafts of control and NGF-secreting fibroblasts. Despite this inhibitory milieu, several axonal classes penetrated control fibroblast grafts, including dorsal column sensory, rubrospinal, and nociceptive axons. Axon growth was amplified more in the presence of NGF-secreting grafts. Confocal microscopy demonstrated that axon growth was, paradoxically, preferentially associated with NG2-rich substrates in both graft types. NG2 expression also increased after sciatic nerve injury, wherein axons successfully regenerate. Cellular sources of NG2 in SCI and peripheral nerve lesion sites included Schwann cells and endothelial cells. Notably, these same cellular sources in lesion sites produced the cell adhesion molecules L1 and laminin, and these molecules all colocalized. Thus, axons grow along substrates coexpressing both inhibitory and permissive molecules, suggesting that regeneration is successful when local permissive signals balance and exceed inhibitory signals. |
| Starting Page | 18 |
| Ending Page | 23 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jneurosci.org/content/jneuro/23/28/9276.full.pdf |
| PubMed reference number | 14561854v1 |
| Volume Number | 23 |
| Issue Number | 28 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abducens Nerve Diseases Axon Cell secretion Chondroitin Sulfate Proteoglycans Chondroitin Sulfates Class Dorsal funiculus Extracellular Matrix Growth Factor Laminin NCAN gene Natural regeneration Peripheral Nerves Protein Tyrosine Phosphatase, Receptor Type Z Proteoglycan Spinal Cord Injuries Structure of sciatic nerve Transplanted tissue Versicans Vocal Cord Paralysis brevican central nervous system tumor, pediatric nerve injury permissiveness |
| Content Type | Text |
| Resource Type | Article |
