Document Detail


Functional regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy.
MedLine Citation:
PMID:  11606629     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lesioned axons within the dorsal roots fail to regenerate through the peripheral nerve transition zone and into the spinal cord. This regenerative failure leads to a persistent loss of sensory function. To induce axonal growth across this barrier, we used recombinant adenovirus to express fibroblast growth factor-2 (FGF2), nerve growth factor (NGF), L1 cell adhesion molecule (L1), or beta-galactosidase (LacZ) within the endogenous glia of the dorsal spinal cord 16 d after injury. Expression of either FGF2 or NGF, but not L1 or LacZ, induced robust axonal regeneration into normal as well as ectopic locations within the dorsal spinal cord. This regeneration led to near-normal recovery of thermal sensory function. Functional recovery and the majority of regenerating axons within the dorsal horn disappeared with recutting of the sensory roots. Injections of adenovirus encoding NGF, but not FGF2, also resulted in extensive sprouting of noninjured sensory axons, which we previously demonstrated could cause hyperalgesia and chronic pain. Thus, neurotrophic factor gene therapy administered as late as 16 d after injury may serve as a useful treatment to elicit recovery after dorsal root avulsion; however, the choice of neurotrophin is important to induce selective regeneration of damaged axons.
Authors:
M I Romero; N Rangappa; M G Garry; G M Smith
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  21     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-18     Completed Date:  2001-12-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8408-16     Citation Subset:  IM    
Affiliation:
Department of Physiology, Spinal Cord and Brain Injury Research Center, University of Kentucky, Albert B. Chandler Medical Center, Lexington, Kentucky 40536-0298, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Afferent Pathways / drug effects,  physiopathology
Animals
Axons / drug effects
Chronic Disease
Disease Models, Animal
Female
Fibroblast Growth Factor 2 / administration & dosage*,  genetics
Gene Therapy / methods*
Genetic Vectors / administration & dosage,  genetics
Leukocyte L1 Antigen Complex
Locomotion / drug effects
Membrane Glycoproteins / administration & dosage,  genetics
Microinjections
Nerve Crush
Nerve Growth Factor / administration & dosage*,  genetics
Neural Cell Adhesion Molecules / administration & dosage,  genetics
Pain Measurement / drug effects
Rats
Rats, Sprague-Dawley
Reaction Time / drug effects
Recovery of Function / drug effects,  physiology
Regeneration / drug effects*
Spinal Cord / drug effects,  pathology,  physiopathology
Spinal Cord Injuries / pathology,  physiopathology,  therapy*
beta-Galactosidase / administration & dosage,  genetics
Grant Support
ID/Acronym/Agency:
GM58057/GM/NIGMS NIH HHS; NS33776/NS/NINDS NIH HHS; NS38126/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Leukocyte L1 Antigen Complex; 0/Membrane Glycoproteins; 0/Neural Cell Adhesion Molecules; 103107-01-3/Fibroblast Growth Factor 2; 9061-61-4/Nerve Growth Factor; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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