Title page for etd-0823111-140424


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URN etd-0823111-140424
Author Jhih-Yin Shi
Author's Email Address No Public.
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Department Biological Sciences
Year 2010
Semester 2
Degree Ph.D.
Type of Document
Language English
Title Glial Cell Line–Derived Neurotrophic Factor Gene Transfer Exerts Protective Effect on Axons in Sciatic Nerve Following Constriction-Induced Peripheral Nerve Injury
Date of Defense 2011-07-08
Page Count 117
Keyword
  • Angiogenesis
  • Diabetes
  • Diabetic neuropathy
  • GDNF
  • Gene delivery
  • Abstract Damage to peripheral nerves following trauma or disease has a number of consequences including burning pain, muscle wasting, paralysis, or organ dysfunction. The most common form of neuropathy is that associated with metabolic abnormality, notably diabetes. Many diabetics, especially those with poor blood sugar control, ultimately develop a distal symmetrical and painful neuropathy that initially affects the longest peripheral axons, but with time spreads proximally. Deficiency in neurotrophic support has been proposed to contribute to the development of diabetic neuropathy. Recently, peripheral gene delivery of vascular endothelial growth factor (VEGF), neurotrophin-3 (NT-3), NGF, BDNF or hepatocyte growth factor (HGF) has been shown to facilitate the continuous production of neurotrophic factors and alleviate the diabetic neuropathy. The role of glial cell-derived neurotrophic factor (GDNF) in the pathogenesis and therapeutics of diabetic neuropathy is not well defined. The main objectives of this research sought to inspect the protective effect of GDNF peripheral gene delivery during hyperglycemia- or constriction- induced sciatic nerve injury in rats. In present proposal, we propose to investigate the change in organization and expressions of GDNF signaling complex in the sciatic nerve following injury in the initial stage. Subsequently, the recombinant adenovirus was used gene delivery system for GDNF to evaluate the potential of intramuscular administration of gene delivery for prevent nerve degeneration, and the molecular mechanism of GDNF to ameliorate neuropathy will be clarified. The above study would enable us to test the hypothesis that the topical gene delivery might be a suitable strategy for the treatment of diabetic neuropathy and other disorders in peripheral nerve. Furthermore, the results of animal studies might be extrapolated for future clinical application.
    Advisory Committee
  • Cheng, Jiin-Tsuey - chair
  • Hsu, Ching-Mei - co-chair
  • Chen, Lee-Wei - co-chair
  • Huang, Hung-Tu - co-chair
  • Tai, ming-hong - advisor
  • Chao, David - advisor
  • Files
  • etd-0823111-140424.pdf
  • indicate access worldwide
    Date of Submission 2011-08-23

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