The goal of this project is to conduct pre-clinical tests of components of the extracellular matrix molecule tenascin-C that offer potential as therapeutics for enhancing nerve fiber regeneration. This may lead to the development of a treatment for spinal cord injury, a devastating condition for which there are no reparative treatments available. The study is based on a new understanding of how the fhA-D component of tenascinC regulates neurite outgrowth. The project will examine effects of delivering fnA-D recombinant protein, or its active peptide sequence (VFDNFVLK ) to the site of an experimental spinal cord injury. Hemisection of the dorsal thoracic (T9) spinal cord of rats will be used to examine the response of corticospinal and primary afferent nerve fibers to transection and treatment with the protein and peptide. Groups of animals will be assigned to treatment with fnA-D, VFDNFVLK, or buffer delivered intrathecally for two weeks from an implanted osmotic pump. Hind limb function will be monitored with a grid-walking test. The primary measure of treatment effect will be immunohistological analysis of axonal regeneration, using Cholera toxin injected either into the motor cortex or into the sciatic nerves. Effects on regeneration of axons will be examined qualitatively and measured quantitatively.
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