{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:53:20Z","timestamp":1793692400450,"version":"4.5.1"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eskisehir Osmangazi University Scientific Research Projects Committee","award":["TSA-2023-2701"],"award-info":[{"award-number":["TSA-2023-2701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The aim was to evaluate nerve healing using immunohistochemical, histological, and functional techniques and to compare the effects of two different therapeutic ozone application methods by perineural and intraperitoneal ozone treatment in rats with a crush injury model of sciatic nerve. Materials and Methods: Forty male Sprague Dawley rats were divided into four subgroups of ten rats each: (1) Control group: The left sciatic nerve incised and closed without crush injury, no treatment; (2) Paralyzed group: Crush injury to the left sciatic nerve, no treatment; (3) Perineural ozone group: Crush injury to the left sciatic nerve, treated with perineural ozone therapy; (4) Intraperitoneal ozone group: Crush injury to the left sciatic nerve, treated with intraperitoneal ozone therapy. The treatments were administered for a 14-day period. Hematoxylin and eosin (H&amp;E) and toluidine blue staining were used for histological examination; TUNEL staining was used for immunohistochemical examination. Pinch test and rotarod performance assessment were utilized for functional evaluation. Results: The pinch test scores showed significant improvement in perineural and intraperitoneal ozone treatment groups after treatment (p &lt; 0.001 and p = 0.003, respectively). The scores of myelin degeneration, vascular congestion, vascular wall thickness, inflammation, and toluidine blue and TUNEL staining were significantly lower in both ozone treatment groups compared to the paralyzed group (p &lt; 0.001). Vascular wall thickness scores were significantly higher in the perineural ozone group compared to the control and intraperitoneal ozone groups (p = 0.004 and p = 0.013, respectively). The Schwann cell proliferation scores were significantly higher in the perineural ozone group compared to the control group and intraperitoneal ozone groups (p &lt; 0.001). Conclusions: Both applications of ozone therapy accelerated the healing of nerve regeneration, reduced inflammation and apoptosis based on histopathological results, and enhanced nerve function in rats with sciatic nerve injury. Perineural ozone therapy has been demonstrated to be an efficacious alternative to systemic ozone treatments in the management of sciatic nerve injury. Further studies are needed to determine optimal ozone dosage and administration protocols for the treatment of nerve injury.<\/jats:p>","DOI":"10.3390\/medicina60122097","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:33:29Z","timestamp":1734928409000},"page":"2097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparison of the Effects of Perineural and Intraperitoneal Ozone Therapy on Nerve Healing in an Experimental Sciatic Nerve Injury Model"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5421-0116","authenticated-orcid":false,"given":"Burcu","family":"Ay\u0131k","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6575-5699","authenticated-orcid":false,"given":"Abdullah","family":"Ortadeveci","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2943-4833","authenticated-orcid":false,"given":"Fulya","family":"Bak\u0131lan","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek Buruko\u011flu","family":"D\u00f6nmez","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1543-2223","authenticated-orcid":false,"given":"Semih","family":"\u00d6z","sequence":"additional","affiliation":[{"name":"Elderly Care, Health Care Services, Vocational School of Health Services, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cengiz","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilmi","family":"\u00d6zden","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Arma\u011fan","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Eski\u015fehir Osmangazi University, Eski\u015fehir 26040, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jneumeth.2015.01.021","article-title":"The sciatic nerve injury model in pre-clinical research","volume":"243","author":"Geuna","year":"2015","journal-title":"J. Neurosci. Methods"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.prp.2011.06.011","article-title":"Curcumin protects the dorsal root ganglion and sciatic nerve after crush in rat","volume":"207","author":"Noorafshan","year":"2011","journal-title":"Pathol. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0894-1130(98)80007-0","article-title":"Peripheral nerve regeneration, repair, and grafting","volume":"11","author":"Dagum","year":"1998","journal-title":"J. Hand Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/micr.1920110311","article-title":"Sensory recovery following digital replantation","volume":"11","author":"Glickman","year":"1990","journal-title":"Microsurgery"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.bjorl.2016.02.009","article-title":"Effects of ozone therapy on facial nerve regeneration","volume":"83","author":"Ozbay","year":"2017","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1177\/159101991101700301","article-title":"Effects of ozone on sciatic nerve in rat","volume":"17","author":"Lin","year":"2011","journal-title":"Interv. Neuroradiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2739\/kurumemedj.MS654002","article-title":"Neuroprotective effects of ozone therapy after sciatic nerve cut injury","volume":"65","author":"Ogut","year":"2018","journal-title":"Kurume Med. J."},{"key":"ref_8","first-page":"69","article-title":"The use of ozone gas for medical purposes","volume":"8","author":"Korkmaz","year":"2009","journal-title":"T\u00fcrk S\u0130lahl\u0131 Kuvvetler\u0130 Koruyucu Hek\u0130ml\u0130k B\u00fclten\u0130"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"450","DOI":"10.2175\/106143010X12851009156088","article-title":"Characteristics transformation of humic acid during ozonation and biofiltration treatment processes","volume":"83","author":"Lin","year":"2011","journal-title":"Water Environ. Res."},{"key":"ref_10","first-page":"105","article-title":"Ozone therapy: Myth and fact","volume":"19","author":"Babuccu","year":"2011","journal-title":"Turkish J. Plast. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1080\/08941939.2017.1369606","article-title":"Ozone partially decreases axonal and myelin damage in an experimental sciatic nerve injury model","volume":"32","author":"Aksel","year":"2019","journal-title":"J. Investig. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/jmcb\/mjw043","article-title":"AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats","volume":"9","author":"Lu","year":"2017","journal-title":"J. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1590\/s0102-865020160110000005","article-title":"Effect of ozone and methylprednisolone treatment following crush type sciatic nerve injury","volume":"31","author":"Ozturk","year":"2016","journal-title":"Acta Cir. Bras."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.wneu.2017.05.161","article-title":"The histological effects of ozone therapy on sciatic nerve crush injury in rats","volume":"105","author":"Somay","year":"2017","journal-title":"World Neurosurg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s00210-018-1521-5","article-title":"Mitigation of cisplatin-induced peripheral neuropathy by canagliflozin in rats","volume":"391","author":"Abdelsameea","year":"2018","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1529-8027.2008.00160.x","article-title":"High-and low-frequency transcutaneous electrical nerve stimulation delay sciatic nerve regeneration after crush lesion in the mouse","volume":"13","author":"Baptista","year":"2008","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_17","first-page":"e3","article-title":"Ischemic preconditioning reduces the severity of ischemia-reperfusion injury of peripheral nerve in rats","volume":"1","author":"Coban","year":"2006","journal-title":"J. Brachial Plex. Peripher. Nerve Inj."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1097\/SAP.0000000000000026","article-title":"An experimental comparison of the effects of propolis, curcumin, and methylprednisolone on crush injuries of the sciatic nerve","volume":"74","author":"Iskdemir","year":"2015","journal-title":"Ann. Plast. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/jbt.20124","article-title":"Biochemical modifications induced in human blood by oxygenation-ozonation","volume":"20","author":"Bocci","year":"2006","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s11255-015-1169-8","article-title":"The effects of ozone therapy on caspase pathways, TNF-\u03b1, and HIF-1\u03b1 in diabetic nephropathy","volume":"48","author":"Erken","year":"2016","journal-title":"Int. Urol. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bonetti, M., Ottaviani, G.M., Simonetti, L., Pellican\u00f2, G., Bonetti, F., and Muto, M. (2023). Treatment of Low-Back Pain with Oxygen-Ozone Therapy. Hernia Updates and Approaches, IntechOpen.","DOI":"10.5772\/intechopen.1001902"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.3390\/brainsci3031182","article-title":"Repair of the peripheral nerve\u2014Remyelination that works","volume":"3","author":"Dahlin","year":"2013","journal-title":"Brain Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pu\u0161nik, L., Ser\u0161a, I., Umek, N., Cvetko, E., and Snoj, \u017d. (2023). Correlation between diffusion tensor indices and fascicular morphometric parameters of peripheral nerve. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1070227"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Manzanera Esteve, I.V., Farinas, A.F., Pollins, A.C., Nussenbaum, M.E., Cardwell, N.L., Kang, H., Does, M.D., Thayer, W.P., and Dortch, R.D. (2019). Probabilistic assessment of nerve regeneration with diffusion MRI in rat models of peripheral nerve trauma. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-56215-2"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/mus.28181","article-title":"Sciatic nerve fascicle differentiation on high-resolution ultrasound with histological verification: An ex vivo study","volume":"70","author":"Snoj","year":"2024","journal-title":"Muscle Nerve"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/2097\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:57:38Z","timestamp":1760115458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/2097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,21]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["medicina60122097"],"URL":"https:\/\/doi.org\/10.3390\/medicina60122097","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,21]]}}}