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Title Glial Cell LineâDerived Neurotrophic Factor Gene Transfer Exerts Protective Effect on Axons in Sciatic Nerve Following Constriction-Induced Peripheral Nerve Injury
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Publication Date
Degree PhD
Discipline/Department Biological Sciences
Degree Level doctoral
University/Publisher NSYSU
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.
Subjects/Keywords Angiogenesis; Diabetes; Diabetic neuropathy; GDNF; Gene delivery
Contributors Huang, Hung-Tu (chair); Chao, David (committee_member); Chen, Lee-Wei (chair); Cheng, Jiin-Tsuey (chair); Tai, ming-hong (committee_member); Hsu, Ching-Mei (chair)
Language en
Rights unrestricted ; Copyright information available at source archive
Country of Publication tw
Format application/pdf
Record ID oai:NSYSU:etd-0823111-140424
Repository nsysu
Date Indexed 2017-05-12
Grantor NSYSU

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