{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:02:28Z","timestamp":1785132148709,"version":"3.55.0"},"reference-count":55,"publisher":"SAGE Publications","issue":"9-10","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"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":[[2026,5,1]]},"abstract":"<jats:p>Spinal trauma caused by contusion or compression is the leading cause of spinal cord injury (SCI) worldwide. These injuries frequently progress to a chronic phase, especially in cases of severe damage. This process results in permanent impairment, affecting both physiological functions and voluntary motor control below the lesion level. At cellular level, the formation of a glial scar, which delineates the cystic cavity, interrupts the connectivity between the central nervous system (CNS) and muscles, as well as the neural communication between the peripheral and CNSs. This process, combined with the CNS inability to promote its self-repair to prevent the progression to a chronic phase, contributes to the exacerbation of spinal cord damage, resulting in a devastating pathology. Currently, there is no effective medical treatment to address the consequences of this condition, apart from physiotherapy, which has variable success depending on the type of injury and the degree of neural tissue preservation in the affected spinal cord. Considering this last, the development of new strategies to promote neuronal repair is essential for reversing this pathology in the future. Therefore, we propose Netrin-1\u2014a developmental guidance molecule known to direct corticospinal tract (CST) growth during CNS development\u2014as a potential therapeutic approach for enhancing neuronal repair in severe chronic SCI. Previously, we demonstrated in an acute phase model of transected SCI that this protein effectively promotes axonal regrowth, axonal reconnection, and recovery of locomotor activity. Based on these findings, we hypothesize that Netrin-1 may additionally act as a neuroreparative molecule in chronic SCI, promoting the recovery of hindlimb movement impaired by injury. To test the therapeutic potential of this molecule, we performed a rat model of chronic SCI with a high-severity lesion at Th10\u2013Th11 thoracic level. We demonstrate that the delivery of Netrin-1 to the epicenter of the lesion promotes significant recovery of extensive movement in the three hindlimb joints, including full flexion and extension, previously impaired by chronic injury. Additionally, it restores functional abilities such as climbing and grasping to some extent. These functional findings correlate with anatomical and cellular observations, including regrowth, sprouting and remyelination of the CST; regrowth\u2013reconnection of extrapyramidal tracts; regrowth\u2013reconnection of serotonergic and dopaminergic axons; prevention of transsynaptic degeneration of lower motoneurons; and neuroprotection of both myelinated sciatic nerve fibers and ascending sensory pathways. In conclusion, this study extends the neuroreparative properties of Netrin-1 to chronic conditions. These findings support its use as potential therapeutic strategy in future human clinical trials.<\/jats:p>","DOI":"10.1177\/08977151251387696","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T08:25:47Z","timestamp":1761812747000},"page":"762-784","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Netrin-1 Therapy Restores Partial Hindlimb Movement in a Rat Model of High-Severity Chronic Spinal Cord Injury"],"prefix":"10.1177","volume":"43","author":[{"given":"Julieta","family":"Schmidt","sequence":"first","affiliation":[{"name":"Laboratorio de Medicina Experimental, \u201cDr. Jorge E. Toblli\u201d Hospital Alem\u00e1n, CABA, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Uceda","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental, \u201cDr. Jorge E. Toblli\u201d Hospital Alem\u00e1n, CABA, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Sgariglia","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental, \u201cDr. Jorge E. Toblli\u201d Hospital Alem\u00e1n, CABA, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Battagino","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Miller School of Medicine, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor Ramiro","family":"Quint\u00e1","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental, \u201cDr. Jorge E. Toblli\u201d Hospital Alem\u00e1n, CABA, Argentina."},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas\u2013CONICET, Buenos Aires, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1682\/JRRD.2008.06.0074"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2023.148484"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200109000-00003"},{"key":"e_1_3_3_5_2","unstructured":"Bickenbach J. International perspectives on spinal cord injury. 2013."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.02.033"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2011.01.024"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.08.013"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22455"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11707-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-024-00352-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0093-5"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12030643"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005972"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2401"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00436-x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81336-7"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2020.7571"},{"key":"e_1_3_3_19_2","volume-title":"Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research (U.S.), National Academies Press (U.S.). Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. (U.S.) Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research (U.S.), National Academies Press (U.S.). Guide for the Care and Use of Laboratory Animals. National Academy Press: Washington, D.C.; 2011."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2021.105294"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31815b7e6b"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-4886(03)00029-3"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.14"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1995.12.1"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-3472(75)90114-1"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.03.024"},{"key":"e_1_3_3_27_2","unstructured":"KINOVEA. KINOVEA. 2023. Available from: www.kinovea.org"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13017"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24243"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-018-0409-0"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06970.x"},{"key":"e_1_3_3_32_2","volume-title":"Chapter 20: Development of Corticospinal Tract Axons: From Embryonic Stage to Adulthood","author":"Quinta HR","year":"2021","unstructured":"Quinta HR. Factors affecting neurodevelopment: Genetics, neurology, behavior, and diet. In: Chapter 20: Development of Corticospinal Tract Axons: From Embryonic Stage to Adulthood. ScienceDirect.com, 2021."},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9544295442"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22774"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.11.007S0889-1591(09)00518-2"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/416636a416636a"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.12.024"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/08977150152693782"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.1991.Supplement_15.12"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.04.030"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.320977"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac5811"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02243.x"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/3506757035067570"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1508-24.2024"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600309"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70193"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0375-x"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91489-n"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047213"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020105537"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.1.64"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1195"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990607)408:3<437::AID-CNE9>3.0.CO;2-5"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000001441"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00350"}],"container-title":["Journal of Neurotrauma"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/08977151251387696","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08977151251387696","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08977151251387696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:18Z","timestamp":1785131358000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/08977151251387696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":55,"journal-issue":{"issue":"9-10","published-print":{"date-parts":[[2026,5,1]]}},"alternative-id":["10.1177\/08977151251387696"],"URL":"https:\/\/doi.org\/10.1177\/08977151251387696","relation":{},"ISSN":["0897-7151","1557-9042"],"issn-type":[{"value":"0897-7151","type":"print"},{"value":"1557-9042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]}}}