Adenoviral nerve growth factor and beta-galactosidase transfer to spinal cord: a behavioral and histological analysis.
OBJECTIVE
The present study characterizes the time course and loci of gene expression induced by the administration of adenoviral vectors into spinal cord. Although a marked inflammatory response to these vectors occurred, no effect on spinal cord function was seen in the 1st postoperative week. The expression of transgenic genes delivered by viral vectors is being exploited throughout the nervous system. The present study utilized adenoviral vectors containing the Rous sarcoma virus (RSV) promoter and a nuclear localization signal to achieve transgenic expression in mammalian spinal cord.


METHODS
Initial experiments utilizing the vector Ad.RSVlacZ (10(12) particles/ml) injected into the region of the central canal resulted in viral gene expression stretching over approximately 1.2 cm of spinal cord. Gene expression was first detected 3 days following viral administration and lasted until postinjection Day 14 with peak expression at Day 7. A variety of cell types in both white and gray matter expressed lacZ. Transgenic expression of the neurotrophin nerve growth factor (NGF) was achieved using injections of Ad.RSVNGF. On histological examination mononuclear inflammatory infiltrate and gliosis were revealed surrounding the injection sites of spinal cords receiving adenovirus but not vehicle. To assess spinal cord function during viral gene expression, animals previously trained in an operant runway task were tested at 7 days postinjection (the peak of viral gene expression) and demonstrated no changes in spinal cord function.


CONCLUSIONS
Results of this study using adenoviral neurotrophic gene transfer indicate that it provided an effective tool for the delivery of potentially therapeutic proteins to the injured or diseased spinal cord.
Division of Neurosurgery, University of Michigan, Ann Arbor 48109, USA.
N M
NM
Boulis
V
V
Bhatia
T I
TI
Brindle
H T
HT
Holman
D J
DJ
Krauss
M
M
Blaivas
J T
JT
Hoff
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D007249:Inflammation; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics* / Q000378:metabolism
D009414:Nerve Growth Factors; D001616:beta-Galactosidase