Table 3.
Summary of experimental design and results contained in articles for regenerative effects on facial nerve injuries according to the neurotrophic factor.
| Potential Substances |
Reference | Animal Model | Surgical Procedures | Experimental Design/Therapeutic Molecules | Evaluations | Results | Conclusions |
|---|---|---|---|---|---|---|---|
| IGF-1 | Sugiyama et al. (2020) [56] | Hartley guinea pigs (n = 12) |
Lt facial nerve compression injury + application of IGF-1 | Group 1: saline controls (n = 6) Group 2: IGF-1 (n = 6) |
-Eyelid closure/CMAP amplitude: 8 weeks after surgery -Histopathologic evaluation: mean number of myelinated axons -qRT‑PCR: IGF‑1 receptor mRNA levels |
-Degree of eyelid closure was greater in Group 2. -Complete recovery rate was greater in Group 2 than Group 1. -CMAP amplitude was positively correlated with the degree of eyelid closure at 8 weeks. IGF-1 receptor mRNA was significantly greater at 7 days after compression than at 2 days. |
Topical intratemporal application of IGF-1 produced a significantly higher complete recovery rate. |
| IGF-1 | Bayrak et al. (2017) [2] | New Zealand rabbits (n = 21) | Rt facial nerve crush injury | Group 1:nerve crush injury alone (n = 7) Group 2: nerve crush injury + saline (n = 7) Group 3: nerve crush injury + IGF-1 (n = 7) |
-CMAP amplitude: 10 and 42 days after surgery -Histological studies |
-CMAP amplitude was significantly lower in Group 2 on day 10 compared with that in Group 3 (p < 0.05). -Axonal order and myelin were preserved, and Schwann cell proliferation was close to normal in Group 3 (p < 0.05). |
Local application of IGF-1 was found to be efficacious in the recovery of a facial nerve crush injury |
| IGF-1 | Matsumine et al. (2016) [61] | Lewis rats (n = 30) | The buccal branch of the Lt facial nerve transection (7 mm defect) + silicone tube | Group 1: silicon tube only (n = 20) Group 2: silicon tube filled with bFGF (n = 10) |
-Transmission electron microscopy: mean axonal density and diameter, myelin thickness | -The rate of nerve regeneration and number of regenerating nerve axons was higher in Group 2, which also showed a better degree of maturation of nerve axons. | bFGF was efficacious in promoting facial nerve regeneration. |
| TGF‑β3 | Wang et al. (2016) [58] | Adult rabbits (n = 20) | The buccal branch of the Lt facial nerve transection (5 mm defect) + silicone tube | Group 1: right silicon tube filled with TGF‑β3 (50 ng/μL) (n = 10) Group 2: left silicon tube filled with saline (n = 10) Group 3: surgical control (n = 10). |
-CMAP amplitude/CMAP latency: 12 weeks after surgery -Electron microscopy: total number and diameter of regenerated nerve fibers |
-The total number and diameter of nerve fibers were significantly increased in the TGF-β3 group, compared with the surgical control group (p < 0.01). -Epineurial repair of facial nerves and nerve fibers was complete. -CMAP amplitude was larger and latency was shorter in Group 1. |
TGF‑β3 may promote the regeneration of facial nerves. |
| Neurotrophin-3 | Wang et al. (2016) [78] | Sprague-Dawley rats(n = 15) | Lt facial nerve crush injury | Group 1: crush injury + NAT-NT- 3 (n = 5) Group 2: crush injury + CBD-NT-3 (n = 5) Group 3: crush injury + sham (n = 5) |
CMAP amplitude Facial nerve function examination Western blotting: NT-3 retention Immunohistochemical staining: collagen content evaluation |
-Exogenous NT-3 levels in the CBD-NT-3 group were significantly higher than those in the NAT-NT-3 group. -Axon growth was more ordered and nerve functional recovery was significantly greater in the CBD-NT-3 group than in the NAT-NT-3 group. |
CBD-NT-3 enhances facial nerve regeneration and functional recovery. |
| Hepatocyte growth factor | Esaki et al. (2011) [73] | Balb/C mice (n = 25) | Rt facial nerve crush injury. HSV-HGF, control vector (HSV-LacZ), or medium (PBS) was then applied to the compressed nerve. | Group 1: crush injury + HSV-HGF (n = 5) Group 2: crush injury + HSV-LacZ (n = 5) Group 3: crush injury + PBS (n = 15) |
Facial functional analysis CMAP amplitude Enzyme-linked immunosorbent assay: HGF concentration Immunohistochemical staining |
-Recovery in the HGF group was significantly faster than that in either the LacZ or PBS group (p < 0.01). -Recovery of CMAP amplitude was greater in the HGF group compared with the LacZ group (p < 0.01). -The number of myelinated nerve fibers was greater in the HGF group than in the LacZ group. |
Introduction of HSV-HGF around the damaged nerve significantly accelerated the recovery of facial nerve function. |
| bFGF | Komobuchi et al. (2010) [63] | Hartley guinea pigs (n = 24) |
Lt facial nerve compression injury + application of bFGF | Group 1: controls (n = 8) Group 2: bFGF single shot (n = 8) Group 3: bFGF-hydrogel (n = 8) |
-Evaluation of facial movements: 6 weeks after surgery -Conduction velocity -Histological evaluation |
-Facial nerve functional recovery was faster and conduction velocity was greater in Group 3 than in Groups 1 or 2 (p < 0.05). -The number of myelinated nerve fibers was significantly larger in Group 3 than in other groups (p < 0.05). |
A bFGF-impregnated biodegradable hydrogel proved to be effective in facilitating recovery. |
| PRP and/or MSCs | Cho et al. (2010) [69] | Albino guinea pigs (n = 24) | The Rt facial nerve transection and anastomosis | Group 1: anastomosed only (n = 6) Group 2: anastomosed + PRP (n = 6) Group 3: anastomosed + nMSCs (n = 6) Group 4: anastomosed + PRP + nMSCs (n = 6) |
-Facial functional analysis -Electrophysiologic evaluation -Neurotrophic factors assay -Histologic evaluation |
-Function and CMAP amplitude were improved in Groups 2–4 compared with the control group 4 weeks after surgery (p < 0.05). -Axon counts and myelin thickness were improved in Groups 2–4. -Group 4 had the greatest number of myelinated axon fibers (p < 0.05). |
PRP and/or nMSCs promote facial nerve regeneration. The combined use of PRP and nMSCs showed a beneficial effect. |
| GDNF | Barras et al. (2009) [65] | Wistar rats (n = 28) | Immediate and delayed grafts (repair 7 months after the lesion). The buccal branch of the Lt facial nerve transection (10 mm defect) + autologous nerve graft |
Group 1: immediate repair, 15-mm autologous graft only (n = 4) Group 2: immediate repair. 12-mm autologous graft + 5-mm channel without GDNF (n = 4) Group 3: immediate repair, 12-mm autologous graft + 5-mm GDNF-releasing channel (n = 6) Group 4: delayed repair, 15-mm autologous graft only (n = 4) Group 5: delayed repair, 12-mm autologous graft + 5-mm channel without GDNF (n = 5) Group 6: delayed repair, 12-mm autologous graft + 5-mm GDNF-releasing channel (n = 5) |
-Facial functional analysis: 3 and 6 weeks after nerve repair -Nerve conduction study -Histological analysis: number of myelinated fibers |
-GDNF promoted an increase in the number and maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. | Application of GDNF to facial nerve grafts via nerve guidance channels improves regeneration after late repair. |
| PRP | Cho et al. (2009) [70] | Albino guinea pigs (n = 14) | The Rt facial nerve transection and anastomosis | Group 1: controls (n = 7) Group 2: fibrin glue +PRP (n = 7) |
-Facial functional analysis -CMAP amplitude-Western blot analysis -Histological evaluation |
-High levels of NT-3, angiopoietin-1, GDNF, NGF, and BDNF were observed in Group 2. -Motor function recovery, CMAP amplitude, and axon count were significantly improved in Group 2. |
PRP improved functional outcome. |
| PRP | Farrag et al. (2007) [72] | Sprague-Dawley rats (n = 49) |
The buccal branch of the Lt facial nerve transection | Group 1: suture only (n = 11) Group 2: PRP only + no suture (n = 5) Group 3: PRP + suture (n = 5) Group 4: PPP + no suture (n = 5) Group 5: PPP + suture (n = 5) Group 6: fibrin sealant + no suture (n = 12) Group 7: fibrin sealant + suture (n = 6) |
-Facial functional analysis -CMAP amplitude/latency/area: presurgery and 8 weeks after surgery -Histomorphometric analysis |
-Overall outcomes were improved in the suturing group (p < 0.05). -The degree of recovery was greater in Group 2 than Group 4 (p < 0.05). -Duration and latency of CMAP and axon counts were most improved in Group 3 compared with suture and PPP-plus-suture groups (p < 0.05). |
The most favorable results were obtained with PRP added to the suture. |
CMAP: Compound muscle action potential; qRT-PCR: quantitative reverse transcription-polymerase chain reaction; IGF-1: insulin-like growth factor 1; NGF: neural growth factor; bFGF: basic fibroblast growth factor; NAT-NT-3: native neurotrophin-3; CBD: collagen-binding domain; MSC: mesenchymal stem cell; BDNF: brain-derived neurotrophic factor; NT-3: neurotrophin-3; HSV-HGF: herpes simplex virus vector that incorporated hepatocyte growth factor; PBS: phosphate-buffered saline; PRP: platelet-rich plasma; PPP: platelet-poor plasma; nMSC: neural-induced mesenchymal stem cell; GDNF: glial cell line-derived neurotrophic factor.