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Peer-reviewedCC BY 4.0Aesthetic Plastic Surgery

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

8 affiliations
  1. 1Faculty of Medicine, Bezmialem Vakıf University, Istanbul, Turkey
  2. 2Faculty of Medicine, Department of Anatomy, Bezmialem Vakıf University, Istanbul, Turkey
  3. 3Faculty of Medicine, Department of Histology and Embryology, Bezmialem Vakıf University, Istanbul, Turkey
  4. 4Nihat Mustafayev Clinic, Istanbul, Turkey
  5. 5Faculty of Medicine, Department of Physical Therapy and Rehabilitation, Cerrahpaşa Istanbul University, Istanbul, Turkey
  6. 6Department of Medical Services and Techniques, Vocational School of Health Services, Pathology Laboratory Techniques Program, Bezmialem Vakıf University, Istanbul, Turkey
  7. 7Faculty of Medicine, Department of Medical Biochemistry, Bezmialem Vakıf University, Istanbul, Turkey
  8. 8Faculty of Medicine, Department of Anatomy, Marmara University, Istanbul, Turkey

Abstract

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.

No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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BibTeX
@article{yılmaz2026dosedependent,
  title = {{Dose-Dependent Effects of Minocycline on Facial Nerve Regeneration: A Microscopic and Molecular Study}},
  author = {Sumera İnci Yılmaz and Sedat Meydan and Mukaddes Eşrefoğlu and Nihat Mustafayev and Leyla Mustafayeva and Kübra Başol Baki and Metin Demirel and Fatih Maral and Şahabettin Selek},
  journal = {Aesthetic Plastic Surgery},
  year = {2026},
  month = aug,
  doi = {10.1007/s00266-026-05976-z},
  url = {https://doi.org/10.1007/s00266-026-05976-z},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Dose-Dependent Effects of Minocycline on Facial Nerve Regeneration: A Microscopic and Molecular Study
AU  - Sumera İnci Yılmaz
AU  - Sedat Meydan
AU  - Mukaddes Eşrefoğlu
AU  - Nihat Mustafayev
AU  - Leyla Mustafayeva
AU  - Kübra Başol Baki
AU  - Metin Demirel
AU  - Fatih Maral
AU  - Şahabettin Selek
PY  - 2026
DA  - 2026/08/06
JO  - Aesthetic Plastic Surgery
DO  - 10.1007/s00266-026-05976-z
UR  - https://doi.org/10.1007/s00266-026-05976-z
AB  - 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.  No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
SN  - 0364-216X
SN  - 1432-5241
ER  -