Document Detail


The differential effects of pathway- versus target-derived glial cell line-derived neurotrophic factor on peripheral nerve regeneration.
MedLine Citation:
PMID:  19943736     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has potent survival effects on central and peripheral nerve populations. The authors examined the differential effects of GDNF following either a sciatic nerve crush injury in mice that overexpressed GDNF in the central or peripheral nervous systems (glial fibrillary acidic protein [GFAP]-GDNF) or in the muscle target (Myo-GDNF).
METHODS: Adult mice (GFAP-GDNF, Myo-GDNF, or wild-type [WT] animals) underwent sciatic nerve crush and were evaluated using histomorphometry and muscle force and power testing. Uninjured WT animals served as controls.
RESULTS: In the sciatic nerve crush, the Myo-GDNF mice demonstrated a higher number of nerve fibers, fiber density, and nerve percentage (p < 0.05) at 2 weeks. The early regenerative response did not result in superlative functional recovery. At 3 weeks, GFAP-GDNF animals exhibit fewer nerve fibers, decreased fiber width, and decreased nerve percentage compared with WT and Myo-GDNF mice (p < 0.05). By 6 weeks, there were no significant differences between groups.
CONCLUSIONS: Peripheral delivery of GDNF resulted in earlier regeneration following sciatic nerve crush injuries than that with central GDNF delivery. Treatment with neurotrophic factors such as GDNF may offer new possibilities for the treatment of peripheral nerve injury.
Authors:
Christina K Magill; Amy M Moore; Ying Yan; Alice Y Tong; Matthew R MacEwan; Andrew Yee; Ayato Hayashi; Daniel A Hunter; Wilson Z Ray; Philip J Johnson; Alexander Parsadanian; Terence M Myckatyn; Susan E Mackinnon
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  113     ISSN:  1933-0693     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-02     Completed Date:  2010-07-26     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  102-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Glial Cell Line-Derived Neurotrophic Factor / pharmacology*
Isometric Contraction / drug effects
Mice
Mice, Transgenic
Motor Endplate / chemistry*
Nerve Crush
Nerve Regeneration / drug effects*
Sciatic Nerve / chemistry*
Grant Support
ID/Acronym/Agency:
R01 NS051706/NS/NINDS NIH HHS; R01 NS051706-04/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Gdnf protein, mouse; 0/Glial Cell Line-Derived Neurotrophic Factor
Comments/Corrections

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