Axonal Regeneration through Regions of Chondroitin Sulfate Proteoglycan Deposition after Spinal Cord Injury: A Balance of Permissiveness and Inhibition

摘要: 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 ECM that inhibit neurite outgrowth in vitro and upregulated injury. We examined growth responses several classes axons this inhibitory environment the presence a cellular fibroblast bridge spinal cord lesion site factor stimulus at (fibroblasts genetically modified secrete NGF). Immunohistochemical analysis showed dense labeling CSPGs NG2, brevican, neurocan, versican, phosphacan host-lesion interface (SCI). Furthermore, robust lesser extent was also observed throughout grafts control NGF-secreting fibroblasts. Despite milieu, penetrated grafts, including dorsal column sensory, rubrospinal, nociceptive axons. Axon amplified more grafts. Confocal microscopy demonstrated axon was, paradoxically, preferentially associated with NG2-rich substrates both graft types. NG2 increased sciatic nerve injury, wherein successfully regenerate. Cellular sources SCI peripheral sites included Schwann cells endothelial cells. Notably, these same produced cell adhesion L1 laminin, all colocalized. Thus, grow along coexpressing permissive molecules, suggesting regeneration successful when local signals balance exceed signals.