Systemic Melatonin Improves Regeneration After Facial Nerve Crush Injury in a Rat Model.

Abstract

Background: Management of facial nerve injuries is challenging, and melatonin has been shown to promote structural and functional neural regeneration.

Purpose: The study's purpose was to measure the regenerative potential of systemic melatonin treatment after facial nerve crush injury.

Study design, setting, sample: This was a double-blind, randomized, controlled study in an animal model conducted at the Bezmialem Vakif University. Twenty-four rats were included in the present study.

Predictor variable: The primary predictor variable was the different doses of systemic melatonin treatment. The animals were randomly divided into 3 treatment groups (n = 8 each): melatonin 5 mg/kg/day, melatonin 20 mg/kg/day, and carrier solution alone (control). The intraperitoneal injections were administered during the 28-day healing period.

Main outcome variable(s): The primary outcome variable was the histomorphometric analysis (mean axonal and Schwann cells density per unit square micrometer). The secondary outcome variable was facial nerve activity assessed by electromyography (amplitude and duration values) and functional observation (whisking biometrics and blinking reflex).

Covariates: None.

Analyses: The normally distributed parameters were evaluated with one-way analysis of variance and Bonferroni post hoc analysis for intergroup comparison. The Fisher exact test and the χ² test were used to examine categorical data.

Results: Histomorphometric analysis revealed that the number of axons with the optimum G-ratio in the control group (180) was statistically significantly lower than expected (217.33; P < .01). The mean axonal density was statistically significantly higher in 5 mg/kg (12.99 ± 2.20/1,000μ²; P = .01) and 20 mg/kg (13.47 ± 1.57/1,000 μ²; P = .004) melatonin treatment groups compared to control group (9.43 ± 2.57/1,000 μ²). Both treatment groups presented higher EMG amplitude (1.59 ± 0.28 for 5 mg/kg melatonin group and 1.94 ± 0.31 for 20 mg/kg melatonin group) than the control group (1.25 ± 0.15; P < .05), and both treatment groups presented shorter duration values (19.16 ± 1.35 for 5 mg/kg melatonin group and 20.39 ± 1.62 for 20 mg/kg melatonin group) than the control group (24.24 ± 3.80; P < .05). Whisking amplitude was statistically significantly higher in 5 mg/kg (61.25 ± 14.28; P = .009) and 20 mg/kg (63 ± 14.69; P = .003) melatonin groups compared to the control group (35.62 ± 8.21) at the end of treatment period.

Conclusion and relevance: Both supraphysiological doses of systemic melatonin treatment enhanced regeneration after facial nerve crush injury in an animal model. Our findings invite further research on the clinical potential of melatonin-induced facial nerve regeneration.