Recombinant human nerve growth factor (rhNGF-β) gene transfer promotes regeneration of crush-injured mental nerve in rats

Abstract

Objective: The aim of this study was to evaluate whether the recombinant human nerve growth factor (rhNGF-β) gene transfer at a crush-injured sensory nerve can enhance nerve regeneration.

Study design: A 4-mm crush injury was made on the mental nerve of mandible in rats, and rhNGF-β adenovirus (6 μL, concentration = 1.0 × 10(11) pfu/μL) was injected at the crushed site for the experimental group (NGF-Ad group, n = 15) and the same volume of PBS for the controls (PBS group, n = 15). A sham group of uninjured nerve was also used for the normal control (Sham group, n = 15). The effect of rhNGF-β adenovirus injection was evaluated by real-time reverse trascriptase polymerase chain reaction for the quantification of nerve growth factor (NGF), low-affinity NGF receptor (p75NTR), and its tyrosine receptor kinase A (trkA) mRNA expression at the trigeminal ganglion (TG) 5 days after injection. Nerve regeneration was evaluated with sensory test, retrograde axonal transport in the TG, and histomorphometric study for 4 weeks.

Results: NGF, p75NTR, and trkA mRNA expression was significantly increased at the TG 5 days after injection of rhNGF-β adenovirus (P < .05). The NGF-Ad group showed improved sensory recovery (P < .05), and the number of retrograde-labeled sensory neurons and soma size of TG were larger compared with the PBS groups (P < .05). Histomorphometrically, the myelinated axon number, myelin thickness, and G-ratio in the NGF-Ad group was also significantly higher than the PBS groups (P < .05).

Conclusions: Recombinant human nerve growth factor gene transfer promoted regeneration of crush-injured mental nerve.