Local administration of neurotrophic growth factor in subcutaneous silicon chambers enhances the regeneration of the sensory component of the rat sciatic nerve

Abstract

An experimental model for local administration of neurotrophic growth factor (NGF) in peripheral nerve lesions is tested. The model consists of a subcutaneous reservoir connected to the sciatic nerve neurorrhaphy. The right sciatic nerves were exposed, severed, and repaired at a level 1.5 cm proximal to their 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 in the nerve neurorrhaphy. Two experimental groups were made: Group A (n = 90) received daily doses of a solution containing NGF-7S during the first 4 weeks after surgery and a single weekly dose thereafter. Within this group, three subgroups of 30 rats each were made: A-4 sacrificed 4 weeks after surgery, A-8 sacrificed after 8 weeks, and A-12 after 12 weeks. Group B (n = 90) received the same vehicle solution without NGF under the same schedule and volume as in Group A. Three subgroups were also made as in Group A depending on the survival period. In order to locate the neurons in the dorsal root ganglia, the retrograde tracer horseradish peroxidase was administered at the proximal stump of the sciatic nerve (tibialis branch), which was severed 1 cm distal to the sciatic trifurcation. In respect of the nonoperated side, the percentage between the number of dorsal root ganglia neurons in the NGF-treated group was significantly higher than in the control group (P < 0.001). These results demonstrate that percutaneous administration of multiple doses of NGF in this model enhances sensory nerve regeneration after sciatic lesions evaluated by horseradish peroxidase labeling of dorsal root ganglia neurons.© 1999 Wiley-Liss, Inc. MICROSURGERY 19:275-280 1999The effect of neurotrophic growth factor (NGF) in the sensory component of a peripheral nerve has been widely documented in the literature. 1-9 Otto et al. 1 prevented the loss of 35% of sensory neurons in the L4-L6 rat dorsal ganglia after axotomy. Using a continuous infusion pump, Gold et al. 5 observed a significant diameter and number increase of the dorsal ganglia fibers. However, Rich et al. 9 reported the most significant differences. After injecting a solution containing NGF (1 mg/ml), they observed a significant increment in the number and percentage of the rat sciatic myelinated axons at 4 weeks, then the number and quality of the regenerated axons can be inferred to the sensorial component. Four years later, Pang et al.6 corroborated in detail the results obtained by Rich et al. In the same year, Derby et al. 7 found that both the proximal and distal nerve stumps regenerated in a guide that contained NGF and were able to cross more of the gap. They also observed a faster regeneration process especially at the first 3 weeks. Observing a prompt sensitive recuperation, they postulated the use of NGF in treatments of peripheral nerve lesions.Different experimental models have been designed to show the efficacy of exogenous administration ...

Acute glucose deprivation leads to apoptosis in a cell model of acute diabetic neuropathy

“…Other neuronal growth factors such as NT3 and NT4/5 have shown neuroprotective effects for auditory system cells (Zheng et al, 1995a ; 1995b ) and DRG neurons ( Gao et al, 1995 ) . In addition, NGF enhances regeneration in peripheral nerve injury models ( Oudega and Hagg, 1999 ; Santos et al, 1999 ) . In our study, NGF prevented cell death, but antioxidants did not.…”

Nerve conduits and growth factor delivery in peripheral nerve repair

“…The drug is filled periodically into the reservoir by means of syringe and needle. The use of an injection device for daily administration of NGF (660 ng) to an epineurial suture of the rat sciatic nerve enhanced nerve regeneration without inducing any device‐related adverse effects ( Santos et al, 1998; 1999 ) . Unfortunately, the authors did not profit from the unique feature of injection devices to apply different delivery regimens, such as those matching the mRNA expression pattern of NGF or its receptors after axotomy.…”

Effect of Platelet-Rich Plasma on Peripheral Nerve Regeneration

“…In contrast, numerous previous experimental studies have demonstrated trophic effects of some factors or agents on the primary anastomosis model. 11,[29][30][31] Local administrations of exogenous factors or agents to the nerve repair site incorporate different methods that aim to produce relatively constant rates of drug release and achieve reliable local concentrations. The most common type of local delivery has been with implantable osmotic pumps.…”