{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T05:16:10Z","timestamp":1766726170103,"version":"3.48.0"},"reference-count":21,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF 2018R1A6A1A03025124"],"award-info":[{"award-number":["NRF 2018R1A6A1A03025124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF 2022R1A2C1091779"],"award-info":[{"award-number":["NRF 2022R1A2C1091779"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea Health Technology R&D Project through the Korea Health Industry Development Institute"},{"name":"Ministry of Health & Welfare, Republic of Korea","award":["RS-2024-00509118"],"award-info":[{"award-number":["RS-2024-00509118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Facial nerve injury from conditions such as Bell\u2019s palsy, trauma, surgery, and infection leads to facial asymmetry and motor deficits. Axotomy models reproduce peripheral nerve disruption and consequent motor impairment. To compare the effects of forward versus reverse autologous nerve suturing on neural regeneration and motor recovery within the facial nucleus after axotomy. Methods: In rats subjected to facial nerve axotomy, motor recovery was assessed at 8 weeks using whisker movement and blink reflex tests. Immunohistochemistry quantified choline acetyltransferase (ChAT), sirtuin 1 (SIRT1), and Iba-1 as indices of cholinergic function, cellular stress\/inflammation modulation, and microglial activation in the facial nucleus. Results: Axotomy significantly reduced whisker and blink scores compared with sham. Both forward and reverse suturing significantly improved these behavioral outcomes versus axotomy. Within the facial nucleus, axotomy decreased ChAT- and SIRT1-positive cells and increased Iba-1 expression, while both suturing techniques increased ChAT and SIRT1 and reduced Iba-1. These changes suggest enhanced cholinergic function, mitigation of stress\/inflammatory responses, and attenuation of microglial activation following repair. Conclusions: Forward and reverse suturing were each associated with improved motor function and favorable molecular and cellular changes in the facial nucleus after facial nerve axotomy. These findings support the utility of surgical repair irrespective of graft orientation and highlight involvement of key pathways\u2014cholinergic signaling, SIRT1-related regulation, and microglial activity\u2014in nerve restoration. This work extends our previous study, which focused on peripheral nerve regeneration after forward and reverse suturing, by elucidating how graft orientation affects central facial nucleus responses. By integrating behavioral outcomes with ChAT, Iba-1, and SIRT1 expression, the present study provides novel insight into the central mechanisms underlying motor recovery after facial nerve repair and helps explain why comparable functional outcomes are achieved regardless of graft polarity.<\/jats:p>","DOI":"10.3390\/jcm15010096","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T03:06:02Z","timestamp":1766718362000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Forward and Reverse Suturing Techniques in Enhancing Neural Regeneration and Motor Function Recovery Following Facial Nerve Axotomy"],"prefix":"10.3390","volume":"15","author":[{"given":"Jae Min","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, School of Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"},{"name":"College of Nursing Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3454-3451","authenticated-orcid":false,"given":"Yeon Ju","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7668","authenticated-orcid":false,"given":"Sung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-0825","authenticated-orcid":false,"given":"Youn-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Nursing Science, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Geun","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, School of Medicine, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.reth.2023.09.012","article-title":"Research Status of Facial Nerve Repair","volume":"24","author":"Huang","year":"2023","journal-title":"Regen. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chojdak-\u0141ukasiewicz, J., and Paradowski, B. (2022). Facial Asymmetry: A Narrative Review of the Most Common Neurological Causes. Symmetry, 14.","DOI":"10.3390\/sym14040737"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ali, S.A., Rosko, A.J., Hanks, J.E., Stebbins, A.W., Alkhalili, O., Hogikyan, N.D., Feldman, E.L., and Brenner, M.J. (2019). Effect of Motor versus Sensory Nerve Autografts on Regeneration and Functional Outcomes of Rat Facial Nerve Reconstruction. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-44342-9"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/micr.30133","article-title":"To Reverse or Not to Reverse? A Systematic Review of Autograft Polarity on Functional Outcomes Following Peripheral Nerve Repair Surgery","volume":"37","author":"Roberts","year":"2017","journal-title":"Microsurgery"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0363-5023(79)80039-8","article-title":"Effect of Nerve Graft Polarity on Nerve Regeneration and Function","volume":"4","author":"Stromberg","year":"1979","journal-title":"J. Hand Surg. Am."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lee, J.M., Chung, J.W., Jeong, N.Y., Jung, J., Kim, S.S., Jeong, S.J., and Yeo, S.G. (2024). Effect of Forward and Reverse Suturing on Nerve Regeneration Following Facial Nerve Axotomy. Biomedicines, 12.","DOI":"10.3390\/biomedicines12112531"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lee, J.-M., Choi, Y.J., Yoo, M.C., and Yeo, S.G. (2023). Central Facial Nervous System Biomolecules Involved in Peripheral Facial Nerve Injury Responses and Potential Therapeutic Strategies. Antioxidants, 12.","DOI":"10.3390\/antiox12051036"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"200","DOI":"10.18240\/ijo.2021.02.04","article-title":"Is Iba-1 Protein Expression a Sensitive Marker for Microglia Activation in Experimental Diabetic Retinopathy?","volume":"14","author":"Shi","year":"2021","journal-title":"Int. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yang, Y., Liu, Y., Wang, Y., Chao, Y., Zhang, J., Jia, Y., Tie, J., and Hu, D. (2022). Regulation of SIRT1 and Its Roles in Inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.831168"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.otot.2022.02.003","article-title":"Nerve Repair and Cable Grafting in Acute Facial Nerve Injury","volume":"33","author":"Razavi","year":"2022","journal-title":"Oper. Tech. Otolayngol. Head Neck Surg."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Grinsell, D., and Keating, C.P. (2014). Peripheral Nerve Reconstruction after Injury: A Review of Clinical and Experimental Therapies. Biomed Res. Int., 2014.","DOI":"10.1155\/2014\/698256"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1055\/s-2002-33323","article-title":"Experimental Study of Polarity in Reversing Cable Nerve Grafts","volume":"18","author":"Nakatsuka","year":"2002","journal-title":"J. Reconstr. Microsurg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s00429-013-0542-6","article-title":"Reduced Cholinergic and Glutamatergic Synaptic Input to Regenerated Motoneurons after Facial Nerve Repair in Rats: Potential Implications for Recovery of Motor Function","volume":"219","author":"Raslan","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lee, J.M., Yoo, M.C., Kim, Y.J., Kim, S.S., and Yeo, S.G. (2024). Expression of ChAT, Iba-1, and NNOS in the Central Nervous System Following Facial Nerve Injury. Antioxidants, 13.","DOI":"10.3390\/antiox13050595"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.brainresrev.2003.11.004","article-title":"The Facial Nerve Axotomy Model","volume":"44","author":"Moran","year":"2004","journal-title":"Brain Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/jnen\/nlad116","article-title":"Restoration of Injured Motoneurons Reduces Microglial Proliferation in the Adult Rat Facial Nucleus","volume":"83","author":"Ishijima","year":"2024","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.3892\/mmr.2016.4948","article-title":"Role of Neuroinflammation in Neurodegenerative Diseases (Review)","volume":"13","author":"Chen","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in Neurodegenerative Disorders: The Roles of Microglia and Astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jiao, F., and Gong, Z. (2020). The Beneficial Roles of SIRT1 in Neuroinflammation-Related Diseases. Oxidative Med. Cell Longev., 2020.","DOI":"10.1155\/2020\/6782872"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Razick, D.I., Akhtar, M., Wen, J., Alam, M., Dean, N., Karabala, M., Ansari, U., Ansari, Z., Tabaie, E., and Siddiqui, S. (2023). The Role of Sirtuin 1 (SIRT1) in Neurodegeneration. Cureus, 15.","DOI":"10.7759\/cureus.40463"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sethi, P., Mehan, S., Khan, Z., Maurya, P.K., Kumar, N., Kumar, A., Tiwari, A., Sharma, T., Das Gupta, G., and Narula, A.S. (2025). The SIRT-1\/Nrf2\/HO-1 Axis: Guardians of Neuronal Health in Neurological Disorders. Behav. 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