{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:19:03Z","timestamp":1783484343426,"version":"3.55.0"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Strategic Research Program for Brain Sciences from the Agency for Medical Research and Development (AMED), Japan","award":["17dm0107117h0002"],"award-info":[{"award-number":["17dm0107117h0002"]}]},{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (MI) is expected to provide a therapeutic impact on spinal cord injury (SCI). On the other hand, treatment with antibody against repulsive guidance molecule-a (RGMa) has been shown to ameliorate motor deficits after SCI in rodents and primates. Facilitating activity of the corticospinal tract (CST) by rTMS following rewiring of CST fibers by anti-RGMa antibody treatment may exert an enhanced effect on motor recovery in a primate model of SCI. To address this issue, we examined whether such a combined therapeutic strategy could contribute to accelerating functional restoration from SCI. In our SCI model, unilateral lesions were made between the C6 and the C7 level. Two macaque monkeys were used for each of the combined therapy and antibody treatment alone, while one monkey was for rTMS alone. The antibody treatment was continuously carried out for four weeks immediately after SCI, and rTMS trials applying a thermoplastic mask and a laser distance meter lasted ten weeks. Behavioral assessment was performed over 14 weeks after SCI to investigate the extent to which motor functions were restored with the antibody treatment and\/or rTMS. While rTMS without the preceding antibody treatment produced no discernible sign for functional recovery, a combination of the antibody and rTMS exhibited a greater effect, especially at an early stage of rTMS trials, on restoration of dexterous hand movements. The present results indicate that rTMS combined with anti-RGMa antibody treatment may exert a synergistic effect on motor recovery from SCI.<\/jats:p>","DOI":"10.1371\/journal.pone.0252023","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T22:50:24Z","timestamp":1622674224000},"page":"e0252023","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["An enhanced therapeutic effect of repetitive transcranial magnetic stimulation combined with antibody treatment in a primate model of spinal cord injury"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6748-9179","authenticated-orcid":true,"given":"Hajime","family":"Yamanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Takata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-8962","authenticated-orcid":true,"given":"Hiroshi","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Isosaka-Yamanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"issue":"12","key":"pone.0252023.ref001","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1016\/j.clinph.2006.06.712","article-title":"A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition","volume":"117","author":"PB Fitzgerald","year":"2006","journal-title":"Clin Neurophysiol"},{"issue":"5","key":"pone.0252023.ref002","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/0924-980X(96)96004-X","article-title":"Use and safety of a new repetitive transcranial magnetic stimulator","volume":"101","author":"EM Wassermann","year":"1996","journal-title":"Electroencephalogr Clin Neurophysiol"},{"issue":"4","key":"pone.0252023.ref003","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s002210000432","article-title":"Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability","volume":"133","author":"F Maeda","year":"2000","journal-title":"Exp Brain Res"},{"issue":"5","key":"pone.0252023.ref004","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/S1388-2457(99)00323-5","article-title":"Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation","volume":"111","author":"F Maeda","year":"2000","journal-title":"Clin Neurophysiol"},{"issue":"11","key":"pone.0252023.ref005","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1016\/j.clinph.2014.05.021","article-title":"Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)","volume":"125","author":"J-P Lefaucheur","year":"2014","journal-title":"Clin Neurophysiol"},{"issue":"6","key":"pone.0252023.ref006","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.clinph.2015.02.001","article-title":"Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. 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