The effects of potential neuroprotective agents on rat facial function recovery following facial nerve injury

Abstract

Objective: To evaluate whether a series of pharmacologic agents with potential neuroprotective effects accelerate and/or improve facial function recovery after facial nerve crush injury.

Study design: Randomized animal study.

Setting: Tertiary care facility.

Methods: Eighty female Wistar-Hannover rats underwent head restraint implantation and daily conditioning. Animals then underwent unilateral crush injury to the main trunk of the facial nerve and were randomized to receive treatment with atorvastatin (n = 10), sildenafil (n = 10), darbepoetin (n = 20), or a corresponding control agent (n = 40). The return of whisking function was tracked throughout the recovery period.

Results: All rats initiated the return of whisking function from nerve crush by day 12. Darbepoetin-treated rats (n = 20) showed significantly improved whisking amplitude and velocity across the recovery period, with several days of significant pairwise differences vs comparable control rats (n = 16) across the first 2 weeks of whisking function return. In contrast, rats treated with sildenafil (n = 10) and atorvastatin (n = 10) did not show significant improvement in whisking function recovery after facial nerve crush compared to controls. By week 8, all darbepoetin-treated animals and comparable nerve crush control animals fully recovered whisking function and were statistically indistinguishable.

Conclusion: Among the 3 potentially neuroprotective agents evaluated, only darbepoetin administration resulted in accelerated recovery of whisking parameters after facial nerve crush injury. Further efforts to define the mechanism of action and translate these findings to the use of darbepoetin in the care of patients with traumatic facial paralysis are needed.

Figure 1

Line graphs showing the effect of treatment with atorvastatin (a, b) and sildenafil (c, d) on whisking amplitude and velocity following facial nerve crush injury, (a, b) There is no difference in whisking amplitude or velocity in the atorvastatin-treated animals (n = 10; plots a–b) compared to matched controls (n = 9) or in the sildenafil-treated animals (n = 10; plots c–d) compared to the matched control animals (n = 10). POD, postoperative day.

Figure 2

Line graphs showing the effect of darbepoetin treatment on whisking amplitude (a) and velocity (b), following facial nerve crush injury, along with a table of associated P values, (a) Whisking amplitude during recovery was statistically higher in animals receiving darbepoetin (n = 20) compared to control animals (n = 16) on postoperative days 15, 18, and 21 when tested across days 13 to 21. (b) Whisking velocity during recovery was statistically higher in animals receiving darbepoetin compared to control animals on postoperative days 15, 18. and 21.