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Title: An investigation into the role of proteoglycans in axonal regeneration
Author: Fidler, P.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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Disabilities arising from spinal cord and brain injuries are permanent, due to the inability of the mammalian central nervous system (CNS) to repair itself. In particular, regenerating axons will not grow through the injury site, where a glial scar has formed. The inhibitory nature of this scar may be largely due to the presence of chondroitin sulphate proteoglycans, which are upregulated after injury. The aim of this thesis was to further our understanding of proteoglycans within the glial scar using biochemical, molecular, immunocytochemical and in vitro methods. Using four astrocyte cell lines, which display a range of axon-inhibiting behaviours, the NG2 proteoglycan was identified as an important neurite inhibitor in Neu7, the most inhibitory cell line. Other laboratories have reported that NG2 is upregulated within a CNS lesion. To identify factors which might control the upregulation of this and other proteoglycans after CNS injury, various cytockines were added to highly purified astrocyte cultures and proteoglycan expression assessed by Western blot analysis. The expression of NG2, neurocan and the CS-56 antigen was regulated by a variety of cytokines, both alone and in combination; the proteolytic processing of neurocan could also be manipulated by cytokines. This suggests that the potential exists to reduce the proteoglycan content of the glial scar by manipulating the activity of cytokines after CNS injury. This thesis also discusses the roles of members of the aggrecan family of proteoglycans (aggrecan, versican, neurocan, brevican), and describes attempts to clone novel members of this family. Also described are preliminary experiments to determine if the newly identified family of Ephs and ephrins are expressed within the glial scar. Finally, evidence is presented suggesting the cellular origin of each chondroitin sulphate proteoglycan within the glial scar.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available