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


METHODS
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.
Department of Oral & Maxillofacial Surgery, School of Dentistry, BinZhou Medical School, Binzhou, China.
Bo-Han
BH
Li
Soung-Min
SM
Kim
Sang Bae
SB
Yoo
Myung-Jin
MJ
Kim
Jeong Won
JW
Jahng
Jong-Ho
JH
Lee
D000256:Adenoviridae; D000818:Animals; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D008340:Mandibular Nerve / Q000601:surgery; D009409:Nerve Crush; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics*; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D011984:Sensory Receptor Cells / Q000502:physiology; D012668:Trigeminal Ganglion / Q000378:metabolism; D061221:Trigeminal Nerve Injuries / Q000601:surgery*
D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; C068313:Ngfr protein, rat; D020932:Nerve Growth Factor; D020917:Receptor, trkA