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The Journal of Neuroscience, February 15, 2003, 23(4):1424
Neurotrophin-3 Expressed In Situ Induces Axonal
Plasticity in the Adult Injured Spinal Cord
Lijun
Zhou1, 2,
Brian J.
Baumgartner1,
Sandra J.
Hill-Felberg1,
Leonard R.
McGowen1, 2, and
H. David
Shine1, 2, 3, 4
1 Department of Neurosurgery, 2 Center for
Cell and Gene Therapy, 3 Division of Neuroscience, and
4 Department of Molecular and Cellular Biology, Baylor
College of Medicine, Houston, Texas 77030
The mammalian CNS lacks the ability to effectively
compensate for injury by the regeneration of damaged axons or axonal
plasticity of intact axons. However, reports suggest that molecular or
cellular manipulations can induce compensatory processes that could
support regeneration or plasticity after trauma. We tested whether
local, sustained release of the neurotrophic factor neurotrophin-3
(NT-3) would support axonal plasticity in the spinal cord distal to the site of injury in rats. The corticospinal tract (CST) was cut unilaterally at the level of the medulla. This avoided excessive inflammation, secondary cell death, vascular disruption, and the release of inhibitory molecules in the lumbar spinal cord. A
replication-defective adenoviral vector (Adv) carrying the NT-3 gene
(Adv.EF -NT3) was delivered to the spinal motoneurons by retrograde
transport through the sciatic nerve. Retrograde transport of the
adenoviral vectors avoided the inflammatory response that would be
associated with direct injection into the spinal cord. Transduction of
spinal motoneurons with Adv.EF-NT3 resulted in a significant
increase in the concentration of NT-3 in the L3-L6 region of the
spinal cord for up to 3 weeks. In animals with a CST lesion, this local expression of NT-3 induced growth of axons from the intact CST across
the midline to the denervated side. If the CST remained intact,
overexpression of NT-3 did not lead to an increase in the number of
axons crossing the midline. These data demonstrate that local,
sustained expression of NT-3 will support axonal plasticity of intact
CST axons after trauma-induced denervation.
Key words:
neurotrophin-3; axonal plasticity; adenoviral
vectors; spinal cord injury; regeneration; NT-3
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341424-08$05.00/0
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