Contusive spinal cord injury often results in demyelination of long tracts, and the prospect of remyelinating these tracts by cell transplantation to achieve a degree of functional recovery is under consideration in man. In this project we propose to study the morphology and electrophysiology of spinal cord axons remyelinated by cell transplantation. The primary demyelinating lesion model will consist of controlled X-irradiation of the lumbar spinal cord followed by intraspinal infections of ethidium bromide; this method produces a reliable demyelinating lesions within the dorsal columns with no endogenous remyelination for 5-6 weeks. After completion of experiments in this model, we will utilize the contusive spinal cord injury model. The following Specific Aims will be addressed: 1) Quantification of Schwann cell remyelination of dorsal column axons: comparison of adult and neonatal cells. 2) Do olfactory ensheathing cells alone, or co-infected with sciatic nerve- derived Schwann cells facilitate remyelination of the EB-X demyelinated spinal cord? 3) Does remyelination induced by induced by transplantation of olfactory ensheathing cells and adult Schwann cells restore electrophysiological function? 4) Does the excitability of primary afferent neurons changes after demyelination and transplant-induced remyelination of the intraspinal processes? 5) Are cell transplantation approaches which are effective for remyelinating chemically-induced demyelinated axons effective in rep airing demyelinated axons in a contusive spinal cord injury model?
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