The field of neuronal transplantation has received a great deal of interest since the 1970's and is currently considered a possible treatment option for both neurodegenerative diseases and spinal cord injury. In this dissertation, fetal neostriatal transplants grafted into the lesioned striatum were studied in both the rat and rhesus monkey. Golgi-impregnation and immunohistochemical techniques were extended to the light and electron microscopic levels to determine the detailed anatomy of the developing striatal implants. Choline acetyltransferase immunoreactive and substance P-like immunoreactive neurons within the rat striatal transplants were morphologically and ultrastructurally similar to normal striatal neurons. When the striatal grafting studies were extended into the rhesus monkey, normal neuronal maturation was demonstrated three months postoperative, both at the light and electron microscopic levels, using various neuroanatomical techniques. From these studies it can be concluded that fetal striatal grafts may be a useful treatment option for Huntington's disease, although numerous difficulties including neuronal degeneration and transplant rejection need to be addressed before this approach is applied in the clinical setting. In a second group of experiments, various approaches to improve autologous bone spinal fusions were studied. Specifically, the utilization of demineralized bone matrix, Type I collagen gel, and recombinant human bone morphogenetic proteins were evaluated for their effects on autologous bone spinal fusions in canines. The study demonstrated that recombinant human bone morphogenetic protein has a strong effect on the amount of bone deposition at the fusion site and, in addition, increases the number of vertebral levels which solidly fuse. The Type I collagen gel appeared to improve the interface between the autologous bone grafts and the host bone, while the demineralized bone matrix had a strong negative effect on the autologous bone graft fusions. Spinal fusion operations in the future will be much more successful if these various methods to improve spinal arthrodesis are utilized to their full potential. It is now clear that reconstruction of the central nervous system and its bony coverings is a real possibility in the very near future, although extensive clinical studies need to be performed before they are widely used in the neurosurgery community.
Thesis (Ph.D.) University of Alaska Fairbanks, 1996
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