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Glial cell line-derived neurotrophic factor gene transfer exerts protective effect on axons in sciatic nerve following constriction-induced peripheral nerve injury

Citation

Shi, JY and Liu, GS and Liu, LF and Kuo, SM and Ton, CH and Wen, ZH and Tee, R and Chen, CH and Huang, HT and Chen, CL and Chao, D and Tai, MH, Glial cell line-derived neurotrophic factor gene transfer exerts protective effect on axons in sciatic nerve following constriction-induced peripheral nerve injury, Human Gene Therapy, 22, (6) pp. 721-731. ISSN 1043-0342 (2011) [Refereed Article]

Copyright Statement

Copyright 2010 Mary Ann Liebert, Inc.

DOI: doi:10.1089/hum.2010.036

Abstract

Damage to peripheral nerves following trauma or neurodegenerative diseases often results in various sensory and motor abnormalities and chronic neuropathic pain. The loss of neurotrophic factor support has been proposed to contribute to the development of peripheral neuropathy. The main objective of this study was to investigate the protective effect of glial cell line-derived neurotrophic factor (GDNF) using peripheral gene delivery in a rat model of constriction-induced peripheral nerve injury. In this study, it was shown that mechanical and thermal hypersensitivity increased on the injured limb at day 7 after chronic constrictive injury (CCI) was induced. The neurological changes were correlated with the structural changes and loss of GDNF/Akt signaling, particularly in the distal stump of the injured sciatic nerve. Subsequently, recombinant adenovirus was employed to evaluate the potential of intramuscular GDNF gene delivery to alleviate the CCI-induced nerve degeneration ad neuropathic pain. After CCI for 3 days, intramuscular injection of adenovirus encoding GDNF (Ad-GDNF) restored the protein level and activity of GDNF/Akt signaling pathway in the sciatic nerve. This was associated with an improved myelination profile and behavioral outcomes in animals with CCI. In conclusion, the present study demonstrates the involvement of GDNF loss in the pathogenesis of CCI-induced neuropathic pain and the therapeutic potential of intramuscular GDNF gene delivery for the treatment of peripheral nerve degeneration.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Medical biotechnology
Research Field:Gene and molecular therapy
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Liu, GS (Associate Professor Guei-Sheung Liu)
ID Code:120842
Year Published:2011
Web of Science® Times Cited:24
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-08-31
Last Modified:2019-01-07
Downloads:0

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