Enhanced functional recovery after proximal nerve root injury by vector-mediated gene transfer.
In order to test the functional implication of herpes simplex virus (HSV) vector-mediated gene transfer after axonal injury, we injected replication-incompetent HSV vectors coding for the anti-apoptotic peptide Bcl-2 and the glial cell-derived neurotrophic factor (GDNF), separately or in combination into ventral spinal cord 30 min after a crush injury to the proximal spinal root that was combined with moderate mechanical traction. HSV-mediated expression of Bcl-2 or GDNF enhanced functional recovery assessed by histologic, electrophysiologic, and behavioral parameters up to 5 months after injury. The most sensitive measure of distal motor function, the sciatic function index, was significantly improved in animals injected with the two vectors together. These results suggest an approach to root trauma that might be used to enhance functional recovery after injury.
Natsume
Atsushi
A
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15217, USA.
Wolfe
Darren
D
Hu
Jian
J
Huang
Shaohua
S
Puskovic
Veljko
V
Glorioso
Joseph C
JC
Fink
David J
DJ
Mata
Marina
M
D000818:Animals; D000870:Anterior Horn Cells / Q000473:pathology / Q000502:physiology; D002470:Cell Survival; D004594:Electrophysiology; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008297:Male; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012584:Sciatic Nerve / Q000473:pathology / Q000502:physiology; D018139:Simplexvirus / Q000235:genetics; D013126:Spinal Nerve Roots / Q000293:injuries* / Q000473:pathology / Q000502:physiology; D013266:Stilbamidines; D013997:Time Factors; D019076:Transgenes
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D013266:Stilbamidines