This project uses the postnatal rat spinal cord as a model to investigate factors which promote and inhibit axonal regeneration in the CNS. Corticospinal (CS) axons grow around partial spinal cord injury at birth. A major difference between CS and DC axons is that only CS axons continue to elongate within the neonatal spinal cord and contain a high level of GAP-43, an integral membrane protein associated with axonal elongation. CS growth does not occur past 6 days after OH injury even though normal axonal elongation and synaptogenesis continue until the third postnatal week. Recent data by others shows that this period of CST growth after spinal injury can be extended until at least 15 days of age by limiting glial proliferation or blocking myelin-associated proteins. The present proposal will determine: 1. Whether cessation of CS growth near 6 days of age is related to environmental changes occurring normally or as a result of spinal injury. The time course of CS growth after OH injury at birth and at 6 days of age will be studied (WGA-HRP anterograde labeling), as well as astroglial proliferation at the lesion site (GFAP immunocytochemistry and 3H-thymidine autoradiography). (Specific Aim 1) 2. Whether the time course of an elevated GAP-43 response in CS axons during normal development and after injury will continue until at least 15 days of age. A decline in GAP-43 level will be used as a marker of the end of the growth period for CS axons (immunocytochemistry using monoclonal antibodies to GAP-43). (Specific Aim 2) 3. Whether several procedures which have enhanced CNS axonal growth in previous experiments (sciatic nerve section, induction of segmental dorsal root sprouting of """"""""sciatic"""""""" DC collaterals, implantation of embryonic spinal cord in the spinal injury site) will reinduce the developmental program for axonal elongation and result in regeneration of """"""""sciatic"""""""" DC axons within the neonatal spinal environment. (GAP-43 immunocytochemistry and choleratoxin-HRP transganglionic labeling of DC axons). (Specific Aim 3 a-d)
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