Rescue and sprouting of motoneurons following ventral root avulsion and reimplantation combined with intraspinal adeno-associated viral vector-mediated expression of glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor

Blits, Bas, Carlstedt, Thomas P., Ruitenberg, Marc Jan, de Winter, Fred, Hermens, Wim T. J. M. C., Dijkhuizen, Paul A., Claasens, Jill W. C., Eggers, Ruben, van der Sluis, Ronald, Tenenbaum, Liliane, Boer, Gerard J. and Verhaagen, Joost (2004) Rescue and sprouting of motoneurons following ventral root avulsion and reimplantation combined with intraspinal adeno-associated viral vector-mediated expression of glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor. Experimental Neurology, 189 2: 303-316. doi:10.1016/j.expneurol.2004.05.014


Author Blits, Bas
Carlstedt, Thomas P.
Ruitenberg, Marc Jan
de Winter, Fred
Hermens, Wim T. J. M. C.
Dijkhuizen, Paul A.
Claasens, Jill W. C.
Eggers, Ruben
van der Sluis, Ronald
Tenenbaum, Liliane
Boer, Gerard J.
Verhaagen, Joost
Title Rescue and sprouting of motoneurons following ventral root avulsion and reimplantation combined with intraspinal adeno-associated viral vector-mediated expression of glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor
Journal name Experimental Neurology   Check publisher's open access policy
ISSN 0014-4886
1090-2430
Publication date 2004-10-01
Sub-type Article (original research)
DOI 10.1016/j.expneurol.2004.05.014
Volume 189
Issue 2
Start page 303
End page 316
Total pages 14
Place of publication New York, U.S.A.
Publisher Academic Press
Language eng
Subject 0601 Biochemistry and Cell Biology
Abstract Following avulsion of a spinal ventral root, motoneurons that project through the avulsed root are axotomized. Avulsion between, for example, L2 and L6 leads to denervation of hind limb muscles. Reimplantation of an avulsed root directed to the motoneuron pool resulted in re-ingrowth of some motor axons. However, most motoneurons display retrograde atrophy and subsequently die. Two neurotrophic factors, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), promote the survival of motoneurons after injury. The long-term delivery of these neurotrophic factors to the motoneurons in the ventral horn of the spinal cord is problematic. One strategy to improve the outcome of the neurosurgical reinsertion of the ventral root following avulsion would involve gene transfer with adeno-associated viral (AAV) vectors encoding these neurotrophic factors near the denervated motoneuron pool. Here, we show that AAV-mediated overexpression of GDNF and BDNF in the spinal cord persisted for at least 16 weeks. At both 1 and 4 months post-lesion AAV-BDNF- and -GDNF-treated animals showed an increased survival of motoneurons, the effect being more prominent at 1 month. AAV vector-mediated overexpression of neurotrophins also promoted the formation of a network of motoneuron fibers in the ventral horn at the avulsed side, but motoneurons failed to extent axons into the reinserted L4 root towards the sciatic nerve nor to improve functional recovery of the hind limbs. This suggests that high levels of neurotrophic factors in the ventral horn promote sprouting, but prevent directional growth of axons of a higher number of surviving motoneurons into the implanted root. Copyright © 2004 Elsevier Inc.
Keyword Spinal cord
Motoneuron
Neurotrophic factor
GDNF
BDNF
Viral vectors
Neuroregeneration
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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