Glial cell line‐derived neurotrophic factor released by synthetic guidance channels promotes facial nerve regeneration in the rat

Abstract

Regeneration of the human facial nerve after lesion is often limited, leading to severe functional impairments, in particular when repair is delayed for several months, when cross-facial nerve grafts have to be performed, or in elderly patients. To improve the outcome, the potential accelerating and maturating effects of the neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) on nerve regeneration were assessed using an axotomy model of the rat facial nerve. One-centimeter-long synthetic guidance channels releasing the neurotrophic factors over several weeks were used to bridge an 8 mm nerve gap, a distance that does not allow regeneration in the absence of growth factors. Nerve cables regenerated in the presence of GDNF showed a large number of myelinated axons 6 weeks after grafting (871 +/- 373, n = 5), whereas only 106 +/- 86 (n = 5) myelinated axons were counted in the presence of NT-3. Retrograde labeling with fluorogold revealed 981 +/- 450 (n = 5) and 53 +/- 38 (n = 5) retrogradely labeled motoneurons in the facial nucleus in the presence of GDNF and NT-3, respectively. No regenerated axons or retrogradely labeled cells were observed in the absence of growth factors (n = 6). These results demonstrate that GDNF, as previously described for the sciatic nerve, a mixed sensory and motor nerve, is also very efficient in promoting regeneration of the facial nerve, an essentially pure motor nerve. GDNF may therefore be useful in improving facial nerve regeneration in the clinic.

Approaches to neural tissue engineering using scaffolds for drug delivery

“…The stability of EVA makes it desirable material choice for delivering drugs over an extended time period. It is commonly used to make microspheres for drug delivery [17][18][19][20][21][22][23], while more recently it has been investigated for other neural tissue engineering applications, such as repair of peripheral nerve injury [24][25][26][27].…”

“…The results of this study suggested that methylcellulose was the most suitable of these three materials for use in drug delivery for peripheral nerve repair. Aebischer and coworkers have done extensive work characterizing the controlled release of a variety of growth factors, including NGF, NT-3, BDNF, and GDNF, from EVA rods [24,26,27]. The drug delivery from these rods was characterized as an initial burst followed by sustained release for 30 days.…”

Hepatocyte growth factor incorporated into herpes simplex virus vector accelerates facial nerve regeneration after crush injury

“…6) and glial cell line-derived growth factor. 7 Although these neurotrophic factors have been shown to promote regeneration of the injured nerve, the functional outcomes have often been limited. 8,9 Hepatocyte growth factor (HGF) is a disulfide-linked heterodimeric protein that was initially purified and cloned as a potent mitogen for hepatocytes 10,11 and a natural ligand for the c-Met protooncogene product.…”

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“…It has been extensively used for drug delivery applications, [36][37][38][39] while more recently it has been investigated for neural tissue engineering applications, such as repair of peripheral nerve injury. [40][41][42] Poly (glycolic acid)/Poly (lactic acid)/Poly (lactic-coglycolic acid): Poly (glycolic acid) (PGA) and poly (lactic acid) (PLA) are biodegradable synthetic polymers, which can be reacted to form the copolymer poly (lactic-co-glycolic acid). [43][44][45] After implantation, the ester bonds in the backbone of the polymer can be hydrolyzed into by-products.…”