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Title: Achieving remyelination in the taiep rat : a model for understanding repair of chronic demyelination
Author: Foote, Alastair Kenneth
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
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This study used the taiep rat to address two issues. Firstly it questioned whether the presence of an astrocytosis and chronically demyclinated axons influenced the ability of OPCs to repopulate OPC depleted tissue. Since OPCs are present in the adult taiep CNS, regions of OPC depletion were created using X-irradiation. It was found that the ability of both endogenous and transplanted OPCs to repopulate the OPC-depleted region was unimpaired by the pathology in the taiep CNS. However it was noted that the rate of repopulation by endogenous adult OPCs in taiep and control animals was even slower than previously reported. The second issue examined was whether remyelination could be achieved in a chronically demyclinated environment. LacZ and GFP labelled OPCs, known to be capable of remyelination, were transplanted into the adult taiep spinal cord. The results demonstrated that axons could be remyelinated, but that remyelination was limited to the site of transplantation due to a failure of repopulation of the demyclinated tissue. Widespread repopulation by transplanted OPCs was achieved by depleting the endogenous OPC population prior to transplantation (using X-irradiation), but remyelination still remained limited to regions close to the transplant site. With the knowledge that chronically demyclinated axons in the taiep rat could be remyelinated, it was hypothesised that cell signals associated with tissue damage at the site of cell implantation drive remyelination and that the absence of these signals distant from the transplant site was the cause of the limited remyelination. This was tested by injecting the saline into taiep CNS which had been repopulated by transplanted OPCs. The result was significant remyelination around the site of injection. By chance some transplanted animals also developed meningitis and in these extensive remyelination was also observed. From these studies one can conclude that a chronically demyclinated environment does not inhibit repopulation of OPC depleted tissue, but that repopulation in adult animals is extremely slow.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available