This project will study CNS axonal regeneraton in the spinal cord of the postnatal rat and in the visual system of the frog, Rana pipiens, using anatomical methods. These are systems where various factors thought to inhibit CNS regeneration in the mammal are minimized or held constant, while others are varied, and where the success of regeneration differs. 3H-proline and autoradiography and horseradish peroxidase histochemistry (HRP) will be used to anterogradely label developing and regenerating axons. HRP and fluorescent compounds will be used to label the cell bodies of these axons. HRP-filled axons will be studied with the electron microscope. Four different types of experiments will be done. 1) Corticospinal tract (CST) axons of the rat are able to grow around a midthoracic spinal overhemisection made in the newborn and 6 day rat. By comparing the ability of CST axons to grow around this lesion when it is made either at a cervical or a midthoracic level at different ages we will determine if only developing uncut CST axons will grow around this injury or if CST axons will regenerate until the time these axons form synaptic connections. 2) To determine if the immaturity of the CNS during the neonatal period allows axonal regeneration to occur, we will determine the ability of ascending nerve tracts to grow around a midthoracic hemisection made in the newborn rat. We will first determine whether neurons axotomized during the neonatal period survive this injury and study the maturity of the ascending spinal projections at birth. The spinal cord will then be midthoracically hemisected at birth and the ability of ascending nerve tracts to grow around this injury will be analyzed. 3) Optic axons regenerate after middiencephalic hemisection in the frog but tectal efferent axons will not regenerate through this same lesion. We will determine if one factor contributing to this difference is the formation of anomalous synaptic connections near the zone of injury by tectal efferents. 4) Anomalous optic axons regenerate to the opposite retina 4-6 weeks after nerve crush in the frog but later disappear. We will determine if these retino-retinal axons are collaterals of axons which also project to normal contralateral optic targets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS014096-10
Application #
3395400
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1977-12-01
Project End
1989-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
10
Fiscal Year
1987
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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