Dose-Dependent Effects of Minocycline on Facial Nerve Regeneration: A Microscopic and Molecular Study

Injuries to the facial nerve present clinical difficulties with frequently unfavorable results. This study uses histological, electrophysiological, and LC-MS/MS-based metabolomic techniques to examine the dose-dependent effects of locally administered minocycline on facial nerve regeneration. For that purpose, the rats were divided into three groups. Following nerve transection and suturing, the rats from Group A received sterile water, those from Group B received 40 μg of minocycline, and those from Group C received 100 μg of minocycline locally on the suture line in 20 μL fibrin gel. Nerve regeneration was evaluated using LC-MS/MS metabolomics and histopathological analyses at the end of the 28th day. Electrophysiological analyses were performed on the 0th day and postoperative 1, 2, and 4 weeks. In the sections of Group A, edema within the myelin sheath and beneath the perineurium were the most conspicuous findings. Vacuolar characteristics within the myelin sheath were also detectable. Groups B and C exhibited preserved architecture with minimal edema. Nerve fiber density was similar across groups (p > 0.05). Metabolomics analyses revealed reduced betaine and elevated proline levels in Group C vs. Group A (p < 0.05). Compound muscle action potential values improved over time, especially in Group B (p = 0.013), peaking at week 2. Both doses of minocycline have been found beneficial on facial nerve regeneration. Although Group C showed superior histological and biochemical outcomes, Group B induced greater clinical and electrophysiological outcomes. We suggest that minocycline is effective on nerve regeneration in a dose-dependent manner.

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