{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:09:04Z","timestamp":1779271744971,"version":"3.51.4"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T00:00:00Z","timestamp":1482451200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T00:00:00Z","timestamp":1482451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peripheral nerve long gap defects are a clinical challenge in the regeneration field. Despite the wide variety of surgical techniques and therapies, autografting is the \u201cgold standard\u201d for peripheral nerve gap reconstruction. The pathological process of Wallerian degeneration from the time of acute injury to efficient regeneration requires several weeks. Regeneration time is critical for nerve reconstruction. Immunological demyelination induced by anti-galactocerebroside antibodies plus guinea pig complement was used to shorten the treatment time. Based on an antigen-antibody complex reaction, the demyelinating agent induced an acute and severe demyelination, leading to the pathological process of Wallerian degeneration during the demyelinating period. This method was used to treat a 12\u2009mm-long sciatic nerve defect in rats. The control groups were injected with one of the demyelinating agent components. The results indicated that anti-galactocerebroside antibodies plus guinea pig complement can significantly shorten treatment time and promote nerve regeneration and functional recovery. In addition, the demyelinating agent can increase the mRNA levels of nerve growth factors and can regulate inflammation. In conclusion, treatment with anti-galactocerebroside antibodies plus guinea pig complement can promote axonal regeneration. This therapy provides a novel method to improve functional recovery in the treatment of long nerve defects.<\/jats:p>","DOI":"10.1038\/srep39828","type":"journal-article","created":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T21:35:36Z","timestamp":1482615336000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Experimental immunological demyelination enhances regeneration in autograft-repaired long peripheral nerve gaps"],"prefix":"10.1038","volume":"6","author":[{"given":"Jun","family":"Ge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangliang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Quan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuojing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,12,23]]},"reference":[{"key":"BFsrep39828_CR1","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1097\/00005373-199807000-00025","volume":"45","author":"J Noble","year":"1998","unstructured":"Noble, J., Munro, C. A., Prasad, V. S. & Midha, R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J. Trauma. 45, 116\u2013122 (1998).","journal-title":"J. Trauma."},{"key":"BFsrep39828_CR2","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1002\/mus.20624","volume":"34","author":"JA Kouyoumdjian","year":"2006","unstructured":"Kouyoumdjian, J. A. Peripheral nerve injuries: a retrospective survey of 456 cases. Muscle Nerve. 34, 785\u2013788 (2006).","journal-title":"Muscle Nerve."},{"key":"BFsrep39828_CR3","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.expneurol.2009.09.009","volume":"223","author":"X Jiang","year":"2010","unstructured":"Jiang, X., Lim, S. H., Mao, H. Q. & Chew, S. Y. Current applications and future perspectives of artificial nerve conduits. Exp Neurol. 223, 86\u2013101 (2010).","journal-title":"Exp Neurol."},{"key":"BFsrep39828_CR4","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1002\/1097-4547(20010115)63:2<214::AID-JNR1014>3.0.CO;2-D","volume":"63","author":"A Valero-Cabr\u00e9","year":"2001","unstructured":"Valero-Cabr\u00e9, A. et al. Superior muscle reinnervation after autologous nerve graft or poly-L-lactide-epsilon-caprolactone (PLC) tube implantation in comparison to silicone tube repair. J. Neurosci Res. 63, 214\u2013223 (2001).","journal-title":"J. Neurosci Res."},{"key":"BFsrep39828_CR5","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1515\/REVNEURO.1996.7.1.47","volume":"7","author":"VB Doolabh","year":"1996","unstructured":"Doolabh, V. B., Hertl, M. C. & Mackinnon, S. E. The role of conduits in nerve repair: a review. Rev Neurosci. 7, 47\u201384 (1996).","journal-title":"Rev Neurosci"},{"key":"BFsrep39828_CR6","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/ar.1120","volume":"263","author":"GR Evans","year":"2001","unstructured":"Evans, G. R. Peripheral nerve injury: a review and approach to tissue enginnered constructs. Anat Rec. 263, 394\u2013404 (2001).","journal-title":"Anat Rec."},{"key":"BFsrep39828_CR7","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3109\/17453678709146461","volume":"58","author":"G Lundborg","year":"1987","unstructured":"Lundborg, G. Nerve regeneration and repair. A review. Acta Orthop Scand. 58, 145\u2013169 (1987).","journal-title":"Acta Orthop Scand"},{"key":"BFsrep39828_CR8","doi-asserted-by":"crossref","unstructured":"Shapira, Y. et al. Comparison of results between chitosan hollow tube and autologous nerve graft in reconstruction of peripheral nerve defect: an experimental study. Microsurgery, doi: 10.1002\/micr.22418 (2015).","DOI":"10.1002\/micr.22418"},{"key":"BFsrep39828_CR9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.pneurobio.2012.05.005","volume":"98","author":"I Allodi","year":"2012","unstructured":"Allodi, I., Udina, E. & Navarro, X. Specificity of peripheral nerve regeneration: interactions at the axon level. Prog Neurobiol. 98, 16\u201337 (2012).","journal-title":"Prog Neurobiol."},{"key":"BFsrep39828_CR10","doi-asserted-by":"publisher","first-page":"7158","DOI":"10.1523\/JNEUROSCI.5812-11.2012","volume":"32","author":"DP Yang","year":"2012","unstructured":"Yang, D. P. et al. p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination. J. Neurosci. 32, 7158\u20137168 (2012).","journal-title":"J. Neurosci."},{"key":"BFsrep39828_CR11","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/(SICI)1097-4598(199707)20:7<858::AID-MUS10>3.0.CO;2-O","volume":"20","author":"J Kobayashi","year":"1997","unstructured":"Kobayashi, J. et al. The effect of duration of muscle denervation on functional recovery in the rat model. Muscle Nerve. 20, 858\u2013866 (1997).","journal-title":"Muscle Nerve."},{"key":"BFsrep39828_CR12","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s12031-013-0026-4","volume":"51","author":"A Zendedel","year":"2013","unstructured":"Zendedel, A., Beyer, C. & Kipp, M. Cuprizone-Induced demyelination as a tool to study remyelination and axonal protection. J. Mol Neurosci. 51, 567\u2013572 (2013).","journal-title":"J. Mol Neurosci."},{"key":"BFsrep39828_CR13","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s00401-009-0591-3","volume":"118","author":"M Kipp","year":"2009","unstructured":"Kipp, M., Clarner, T., Dang, J., Copray, S. & Beyer, C. The cuprizone animal model: new insights into an old story. Acta Neuropathol. 118, 723\u2013736 (2009).","journal-title":"Acta Neuropathol."},{"key":"BFsrep39828_CR14","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1097\/PRS.0b013e3181a65a27","volume":"123","author":"AM Kosins","year":"2009","unstructured":"Kosins, A. M. et al. A novel model to measure the regenerative potential of the peripheral nervous system after experimental immunological demyelination. Plast Reconstr Surg. 123, 1688\u20131696 (2009).","journal-title":"Plast Reconstr Surg"},{"key":"BFsrep39828_CR15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1750-1164-7-5","volume":"7","author":"RK Nath","year":"2013","unstructured":"Nath, R. K., Kumar, N. & Somasundaram, C. Modified quad surgery significantly improves the median nerve conduction and functional outcomes in obstetric brachial plexus nerve injury. Ann Surg Innov Res. 7, 5 (2013).","journal-title":"Ann Surg Innov Res"},{"key":"BFsrep39828_CR16","doi-asserted-by":"publisher","first-page":"204173141348103","DOI":"10.1177\/2041731413481036","volume":"4","author":"IC Liao","year":"2013","unstructured":"Liao, I. C. et al. Preclinical evaluations of acellular biological conduits for peripheral nerve regeneration. J. Tissue Eng. 4, 2041731413481036 (2013).","journal-title":"J. Tissue Eng."},{"key":"BFsrep39828_CR17","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1098\/rsif.2011.0009","volume":"8","author":"SW Hsiang","year":"2011","unstructured":"Hsiang, S. W. et al. Novel use of biodegradable casein conduits for guided peripheral nerve regeneration. J. R Soc Interface. 8, 1622\u20131634 (2011).","journal-title":"J. R Soc Interface."},{"key":"BFsrep39828_CR18","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.neulet.2012.03.041","volume":"516","author":"AM McGrath","year":"2012","unstructured":"McGrath, A. M. et al. Fibrin conduit supplemented with human mesenchymal stem cells and immunosuppressive treatment enhances regeneration after peripheral nerve injury. Neurosci Lett. 516, 171\u2013176 (2012).","journal-title":"Neurosci Lett."},{"key":"BFsrep39828_CR19","doi-asserted-by":"publisher","first-page":"8780","DOI":"10.1016\/j.biomaterials.2014.06.049","volume":"35","author":"A Li","year":"2014","unstructured":"Li, A. et al. A bioengineered peripheral nerve construct using aligned peptide amphiphilenanofibers. Biomaterials. 35, 8780\u20138790 (2014).","journal-title":"Biomaterials."},{"key":"BFsrep39828_CR20","first-page":"196","volume":"17","author":"ZH Zhang","year":"2013","unstructured":"Zhang, Z. H. et al. Clinical observation of peripheral nerve injury in 2 patients with cancer after radiotherapy. Contemp Oncol (Pozn). 17, 196\u2013199 (2013).","journal-title":"Contemp Oncol (Pozn)"},{"key":"BFsrep39828_CR21","doi-asserted-by":"publisher","first-page":"e67921","DOI":"10.1371\/journal.pone.0067921","volume":"8","author":"Z Wang","year":"2013","unstructured":"Wang, Z. et al. Hedysari extract improves regeneration after peripheral nerve injury by enhancing the amplification effect. Plos one. 8, e67921 (2013).","journal-title":"Plos one."},{"key":"BFsrep39828_CR22","first-page":"876327","volume":"2013","author":"SC Lee","year":"2013","unstructured":"Lee, S. C., Tsai, C. C., Yao, C. H., Chen, Y. S. & Wu, M. C. Ferulic Acid enhances peripheral nerve regeneration across Long gaps. Evid Based Complement Alternat Med. 2013, 876327 (2013).","journal-title":"Evid Based Complement Alternat Med"},{"key":"BFsrep39828_CR23","doi-asserted-by":"publisher","first-page":"e65034","DOI":"10.1371\/journal.pone.0065034","volume":"8","author":"JF Chabas","year":"2013","unstructured":"Chabas, J. F. et al. Cholecalciferol (vitamin D3) improves myelination and recovery after nerve injury. Plos one. 8, e65034 (2013).","journal-title":"Plos one."},{"key":"BFsrep39828_CR24","first-page":"39","volume":"14","author":"S Zarbakhsh","year":"2012","unstructured":"Zarbakhsh, S. et al. The effects of Schwann and bone marrow stromal stem cells on sciatic nerve injury in rat: a comparison of functional recovery. Cell J. 14, 39\u201346 (2012).","journal-title":"Cell J"},{"key":"BFsrep39828_CR25","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/1742-2094-9-176","volume":"9","author":"E Ydens","year":"2012","unstructured":"Ydens, E. et al. Acute injury in the peripheral nervous system triggers an alternative macrophage response. J. Neuroinflammation. 9, 176 (2012).","journal-title":"J. Neuroinflammation"},{"key":"BFsrep39828_CR26","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1097\/PRS.0b013e31820cf2b0","volume":"127","author":"AM Kosins","year":"2011","unstructured":"Kosins, A. M. et al. Improvement of peripheral nerve regeneration following immunological demyelination in vivo. Plast Reconstr Surg. 127, 1813\u20131819 (2011).","journal-title":"Plast Reconstr Surg"},{"key":"BFsrep39828_CR27","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1097\/SAP.0b013e31823dce7e","volume":"68","author":"AM Kosins","year":"2012","unstructured":"Kosins, A. M., Scholz, T., Lin, M., Evans, G. R. & Keirstead, H. S. Immunological demyelination enhances nerve regeneration after acute transection injury in the adult rat sciatic nerve. Ann Plast Surg. 68, 290\u2013294 (2012).","journal-title":"Ann Plast Surg"},{"key":"BFsrep39828_CR28","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1089\/neu.2008.0732","volume":"26","author":"J Huang","year":"2009","unstructured":"Huang, J. et al. Electrical stimulation accelerates motor functional recovery in autograft-repaired 10\u2009mm femoral nerve gap in rats. J. Neurotrauma. 26, 1805\u20131813 (2009).","journal-title":"J. Neurotrauma."},{"key":"BFsrep39828_CR29","doi-asserted-by":"publisher","first-page":"7248","DOI":"10.1016\/j.actbio.2013.03.024","volume":"9","author":"Y Wang","year":"2013","unstructured":"Wang, Y. et al. A synthetic oxygen carrier in fibrin matrices promotes sciatic nerve regeneration in rats. Acta Biomater. 9, 7248\u20137263 (2013).","journal-title":"Acta Biomater."},{"key":"BFsrep39828_CR30","doi-asserted-by":"publisher","first-page":"e56484","DOI":"10.1371\/journal.pone.0056484","volume":"8","author":"S Jonsson","year":"2013","unstructured":"Jonsson, S. et al. Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery. Plos one. 8, e56484 (2013).","journal-title":"Plos one."},{"key":"BFsrep39828_CR31","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1523\/JNEUROSCI.3371-11.2012","volume":"32","author":"SJ Gladman","year":"2012","unstructured":"Gladman, S. J. et al. Improved outcome after peripheral nerve injury in mice with increased levels of endogenous omega-3 polyunsaturated fatty acids. J. Neurosci. 32, 563\u2013571 (2012).","journal-title":"J. Neurosci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep39828.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39828","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39828.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T07:19:00Z","timestamp":1672903140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep39828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,23]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep39828"],"URL":"https:\/\/doi.org\/10.1038\/srep39828","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,23]]},"assertion":[{"value":"3 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39828"}}