Regeneration of the Motor Component of the Rat Sciatic Nerve with Local Administration of Neurotrophic Growth Factor in Silicone Chambers

ABSTRACT

The experimental model reported consists of a subcutaneous reservoir connected to a rat sciatic nerve anastomosis. The right sciatic nerve was exposed, severed, and repaired at a level 1.5 cm proximal to its trifurcation. Then, a dome-shaped silicone reservoir, connected to the proximal end of a silicone tube, was placed subcutaneously in the dorsum of the experimental animal. The distal end of the connecting tube was located at the nerve anastomosis. There were two experimental groups: Group A animals (n=90) received daily doses of a solution containing nerve growth factor (NGF)-7S during the first 4 weeks after surgery and a single weekly dose thereafter. Within this group, there were three subgroups of 30 rats each: A-4 sacrificed at 4 weeks after surgery; A-8 sacrificed at 8 weeks; and A-12 at 12 weeks. Group B animals (n=90) received the same vehicle solution without NGF at the same schedule and volumes as in Group A. There were also three subgroups as in Group A, depending on the survival period: B-4 (n=30); B-8 (n=30); and B-12 (n=30). In order to localize the motoneurons in the spinal cord, the retrograde tracer, horseradish peroxidase (HRP), was administered at the proximal stump of the sciatic nerve (tib-ialis branch) that was severed 1 cm distal to the sciatic trifurcation (1.5 cm distal to the nerve anastomosis). The number of spinal neurons in the NGF-treated group was statistically significantly higher than in the control group (p <0.001). These results demonstrate that percutaneous administration of multiple doses of neurotrophic growth factor in this model enhances motor nerve regeneration after sciatic lesions, evaluated by HRP-labeling of spinal motoneurons.