{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:27:37Z","timestamp":1790497657888,"version":"4.1.0"},"reference-count":78,"publisher":"SAGE Publications","issue":"15","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Neuroimmune dysfunction is thought to promote the development of several acute and chronic complications in spinal cord injury (SCI) patients. Putative roles for adrenal stress hormones and catecholamines are increasingly being recognized, yet how these adversely affect peripheral tissue homeostasis and repair under SCI conditions remains elusive. Here, we investigated their influence in a mouse model of SCI with acquired neurogenic heterotopic ossification. We show that spinal cord lesions differentially influence muscular regeneration in a level-dependent manner and through a complex multi-step process that creates an osteopermissive environment within the first hours of injury. This cascade of events is shown to critically involve adrenergic signals and drive the acute release of the neuropeptide, substance P. Our findings generate new insights into the kinetics and processes that govern SCI-induced deregulations in skeletal muscle homeostasis and regeneration, thereby aiding the development of sequential therapeutic strategies that can prevent or attenuate neuromusculoskeletal complications in SCI patients.<\/jats:p>","DOI":"10.1089\/neu.2021.0058","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T10:54:48Z","timestamp":1619693688000},"page":"2162-2175","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Local and Systemic Factors Drive Ectopic Osteogenesis in Regenerating Muscles of Spinal-Cord\u2013Injured Mice in a Lesion-Level\u2013Dependent Manner"],"prefix":"10.1177","volume":"38","author":[{"given":"Charlotte","family":"Debaud","sequence":"first","affiliation":[{"name":"Mater Research Institute\u2013The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia."},{"name":"Spine Division, Orthopaedic Surgery Department, Queensland Health, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia."},{"name":"Universit\u00e9 de Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Sant\u00e9\u2013Simone Veil, Montigny-le-Bretonneux, France."},{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Saint Lucia, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu-Wen","family":"Tseng","sequence":"additional","affiliation":[{"name":"Mater Research Institute\u2013The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malha","family":"Chedik","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Sant\u00e9\u2013Simone Veil, Montigny-le-Bretonneux, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kulina","sequence":"additional","affiliation":[{"name":"Mater Research Institute\u2013The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Gen\u00eat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Sant\u00e9\u2013Simone Veil, Montigny-le-Bretonneux, France."},{"name":"Service de R\u00e9habilitation, H\u00f4pital Raymond Poincar\u00e9, APHP, CIC-IT 1429, Garches, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J.","family":"Ruitenberg","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Saint Lucia, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Levesque","sequence":"additional","affiliation":[{"name":"Mater Research Institute\u2013The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2011.05.024"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.5312\/wjo.v6.i1.24"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-5-46"},{"key":"e_1_3_6_5_2","first-page":"272","article-title":"The para-articular ossifications in our paraplegics and tetraplegics: a survey of 704 patients","volume":"16","author":"Hernandez A.M.","year":"1978","unstructured":"Hernandez A.M., , Forner J.V., , de la Fuente T., , Gonzalez C., , and Miro R. (1978). The para-articular ossifications in our paraplegics and tetraplegics: a survey of 704 patients. Paraplegia, 16, 272\u2013275.","journal-title":"Paraplegia"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.74B2.1544955"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31825ee81b"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","unstructured":"Carpentier V.T. Salga M. Gatin L. Gen\u00eat F. and Paquereau J. (2021). Early diagnosis of heterotopic ossification among patients admitted to a neurological post intensive care rehabilitation unit. Eur. J. Phys. Rehabil. Med. doi: 10.2373\/6\/S1973-9087.21.06589-8.","DOI":"10.2373\/6\/S1973-9087.21.06589-8"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10172"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.122"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54986-2"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000000838"},{"key":"e_1_3_6_13_2","first-page":"38","article-title":"Current facts of para-osteo-arthropathy (POA)","volume":"11","author":"Rossier A.B.","year":"1973","unstructured":"Rossier A.B., , Bussat P., , Infante F., , Zender R., , Courvoisier B., , Muhelm G., , Donath A., , Vasey H., , Taillard W., , Lagier R., , Gabbiani G., , Baud C.A., , Pouezat J.A., , Very J.M., , and Hachen H.J. (1973). Current facts of para-osteo-arthropathy (POA). Paraplegia, 11, 38\u201378.","journal-title":"Paraplegia"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1148\/123.1.217"},{"key":"e_1_3_6_15_2","first-page":"346","article-title":"Heterotopic ossification","volume":"43","author":"Dia S.","year":"2002","unstructured":"Dia S., , Elgazzar A.H., , and Collier B.D. (2002). Heterotopic ossification. J. Nucl. Med. 43, 346\u2013353.","journal-title":"J. Nucl. Med"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3101309"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00256-005-0958-z"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/16501970510027628"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016632"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.23.2000152"},{"key":"e_1_3_6_21_2","first-page":"125","article-title":"Heterotopic bone formation: clinical, laboratory, and imaging correlation","volume":"26","author":"Orzel J.A.","year":"1985","unstructured":"Orzel J.A., , and Rudd T.G. (1985). Heterotopic bone formation: clinical, laboratory, and imaging correlation. J. Nucl. Med. 26, 125\u2013132.","journal-title":"J. Nucl. Med"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.12.006"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-020-00636-w"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2017.10.002"},{"key":"e_1_3_6_25_2","first-page":"230","article-title":"Heterotopic ossification following traumatic brain injury and spinal cord injury: insight into the etiology and pathophysiology","volume":"12","author":"Sakellariou V.I.","year":"2012","unstructured":"Sakellariou V.I., , Grigoriou E., , Mavrogenis A.F., , Soucacos P.N., , and Papagelopoulos P.J. (2012). Heterotopic ossification following traumatic brain injury and spinal cord injury: insight into the etiology and pathophysiology. J. Musculoskelet. Neuronal Interact. 12, 230\u2013240.","journal-title":"J. Musculoskelet. Neuronal Interact"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00194"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12552"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182454"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4519"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.96034"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00377"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000412"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4643"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1089\/08977150360547099"},{"key":"e_1_3_6_35_2","first-page":"528","article-title":"Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats","volume":"47","author":"van Eerd J.E.M.","year":"2006","unstructured":"van Eerd J.E.M., , Vegt E., , Wetzels J.F.M., , Russel F.G.M., , Masereeuw R., , Corstens F.H.M., , Oyen W.J.G., , and Boerman O.C. (2006). Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats. J. Nucl. Med. 47, 528\u2013533.","journal-title":"J. Nucl. Med"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470942390.mo110217"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.041"},{"key":"e_1_3_6_38_2","volume-title":"Sympathoadrenal system: neural arm of the stress response, in: Encyclopedia of Neuroscience, 1st","author":"Palk\u00f3vits M.","year":"2010","unstructured":"Palk\u00f3vits M. (2010). Sympathoadrenal system: neural arm of the stress response, in: Encyclopedia of Neuroscience, 1st ed. L.R. Squire (ed). Elsevier: Amsterdam, The Netherlands, pps. 679\u2013684."},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2018.00127"},{"key":"e_1_3_6_40_2","first-page":"327","article-title":"Catecholamines, steroids and immune alterations in ischemic stroke and other acute diseases","volume":"5","author":"Schulze J.","year":"2014","unstructured":"Schulze J., , Vogelgesang A., , and Dressel A. (2014). Catecholamines, steroids and immune alterations in ischemic stroke and other acute diseases. Aging Dis. 5, 327\u2013339.","journal-title":"Aging Dis"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2017.02.004"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/emermed-2016-205780"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986706777584997"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2243-8"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.01.008"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-6997(25)06677-3"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104850"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2009.05312.x"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/sc.2013.136"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.08.021"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0709-736"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0736-y"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.002113"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00042"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9079083"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/sc.1973.32"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2016.08.010"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-018-0027-6"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14172-4"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00164"},{"key":"e_1_3_6_61_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801429RR"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00028.2007"},{"key":"e_1_3_6_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007041"},{"key":"e_1_3_6_64_2","first-page":"41","article-title":"Cardiotoxins from cobra venoms: possible mechanisms of action","volume":"4","author":"Harvey A.L.","year":"1985","unstructured":"Harvey A.L. (1985). Cardiotoxins from cobra venoms: possible mechanisms of action. J. Toxicol. 4, 41\u201369.","journal-title":"J. Toxicol"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)30469-6"},{"key":"e_1_3_6_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20061"},{"key":"e_1_3_6_67_2","article-title":"Blocking neurogenic inflammation for the treatment of acute disorders of the central nervous system","volume":"2013","author":"Lewis K.M.","year":"2013","unstructured":"Lewis K.M., , Turner R.J., , and Vink R. (2013). Blocking neurogenic inflammation for the treatment of acute disorders of the central nervous system. Int. J. Inflam. 2013, 578480.","journal-title":"Int. J. Inflam"},{"key":"e_1_3_6_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23833"},{"key":"e_1_3_6_69_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00027903"},{"key":"e_1_3_6_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201544109"},{"key":"e_1_3_6_71_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010055"},{"key":"e_1_3_6_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-8673.1993.tb00396.x"},{"key":"e_1_3_6_73_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2238-14.2014"},{"key":"e_1_3_6_74_2","first-page":"37","article-title":"Muscle fiber composition in patients with traumatic cord lesion","volume":"8","author":"Grimby G.","year":"1976","unstructured":"Grimby G., , Broberg C., , Krotkiewska I., , and Krotkiewski M. (1976). Muscle fiber composition in patients with traumatic cord lesion. Scand. J. Rehabil. Med. 8, 37\u201342.","journal-title":"Scand. J. Rehabil. Med"},{"key":"e_1_3_6_75_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-017-0400-1"},{"key":"e_1_3_6_76_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.000247.2001"},{"key":"e_1_3_6_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.03.017"},{"key":"e_1_3_6_78_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00352"},{"key":"e_1_3_6_79_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-018-4039-0"}],"container-title":["Journal of Neurotrauma"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/neu.2021.0058","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/neu.2021.0058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/neu.2021.0058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T22:38:38Z","timestamp":1777675118000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/neu.2021.0058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,15]]},"references-count":78,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1089\/neu.2021.0058"],"URL":"https:\/\/doi.org\/10.1089\/neu.2021.0058","relation":{},"ISSN":["0897-7151","1557-9042"],"issn-type":[{"value":"0897-7151","type":"print"},{"value":"1557-9042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,15]]}}}