Spinal cord injury is a devastating clinical problem, and can lead to permanent motor and sensory loss. At the cellular level, the most debilitating consequences of cord injury are not generally associated withy loss of spinal cord neurons per se, but rather from loss of axons that carry crucial motor and sensory information up and down the cord and to the brain. Olfactory ensheathing cells have been postulated to provide a high degree of axonal elongation, based on tests of only a few types of neurons. We propose to test the hypothesis that olfactory ensheathing cells will enhance axonal growth and synapse formation of additional cell types that send axons up and down the spinal cord. We will use an immortalized ensheathing cell line to test the hypothesis that, after infection into the cord, ensheathing cells will enhance axonal growth, but will not lead to further problems associated with unchecked cell division. We will test the hypothesis that the mechanisms by which ensheathing cells act is mediated both by cell surface molecules that enhance axonal extension, and by the release of trophic factors that enhance neuronal growth and survival. As the ultimate goal of these types of experiments is to provide a milieu for axonal growth in the human, we will continue our work studying interspecies facilitation of neurite elongation, and will examine axonal growth of human neurons of rodent olfactory ensheathing cells. Using time lapse digital imaging, we will also test the hypothesis that ensheathing cells can growth into cellular environments that are generally inhospitable to axonal growth, and then accompany axons across them. In order to study axonal regrowth after injury, we have developed a new model utilizing a transgene mouse that expresses the jellyfish green fluorescent protein in a restricted subset of neurons and their axons. These neurons therefore synthesize their own axonal marker, and can be identified in living and fixed cells in the cord and in culture. We will use their transgenic mouse to study the attributes of olfactory ensheathing cells in enhancing axonal recovery after cord injury.
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