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)

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS014096-15
Application #
3395409
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1977-12-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1994-07-31
Support Year
15
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Upstate Medical University
Department
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Dent, L J; McCasland, J S; Stelzner, D J (1996) Attempts to facilitate dorsal column axonal regeneration in a neonatal spinal environment. J Comp Neurol 372:435-56
Maier, D L; Kalb, R G; Stelzner, D J (1995) NMDA antagonism during development extends sparing of hindlimb function to older spinally transected rats. Brain Res Dev Brain Res 87:135-44
Firkins, S S; Bates, C A; Stelzner, D J (1993) Corticospinal tract plasticity and astroglial reactivity after cervical spinal injury in the postnatal rat. Exp Neurol 120:1-15
Bates, C A; Stelzner, D J (1993) Extension and regeneration of corticospinal axons after early spinal injury and the maintenance of corticospinal topography. Exp Neurol 123:106-17
Stelzner, D J; Cullen, J M (1991) Do propriospinal projections contribute to hindlimb recovery when all long tracts are cut in neonatal or weanling rats? Exp Neurol 114:193-205
Hung, Y H; Stelzner, D J (1991) Frog tectal efferent axons fail to regenerate within the CNS but grow within peripheral nerve implants. Exp Neurol 112:273-83
Lahr, S P; Stelzner, D J (1990) Anatomical studies of dorsal column axons and dorsal root ganglion cells after spinal cord injury in the newborn rat. J Comp Neurol 293:377-98
Stelzner, D J; Strauss, J A (1988) Increase in ganglion cell size after optic nerve regeneration in the frog, Rana pipiens. Exp Neurol 100:210-5
Sosale, A; Robson, J A; Stelzner, D J (1988) Laminin distribution during corticospinal tract development and after spinal cord injury. Exp Neurol 102:14-22
Cummings, J P; Stelzner, D J (1988) Effect of spinal cord transection in the newborn, weanling, and adult rat on the morphology of thoracic motoneurons. Exp Neurol 100:381-93

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