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This translational disconnect stems from a fidelity paradox. The over\u2010reliance on rodent models that achieve biomechanical mimicry of human trauma but lack fundamental biological equivalence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated how physical simulation masks critical interspecies divergences. Following PRISMA guidelines, we systematically searched PubMed and Web of Science (2000\u20132024) to assess preclinical model utilization frequencies and synthesized evidence across distinct pathophysiological pillars to evaluate cross\u2010species biological mismatches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis reveals profound spatiotemporal dissonances across three pillars: (i) immunodynamics, where the delayed inflammatory resolution in mice misaligns with human chronobiology; (ii) lesion architecture, distinguishing rodent cystic cavitation from the fibrotic scarring characteristic of human pathology; and (iii) neural circuitry, contrasting indirect rodent corticospinal projections with the direct cortico\u2010motoneuronal connections essential for human dexterity. To address this, we propose a mechanistic fidelity matching framework. This paradigm shifts from indiscriminate single\u2010model validation to a problem\u2010driven matrix, selecting models based on their specific biological fidelity to targeted mechanisms\u2014utilizing mice for scar modulation, rats for cystic repair, and nonhuman primates for fine sensorimotor recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Restoring translational credibility requires replacing the pursuit of a universal model with a hierarchical, cross\u2010species validation pipeline anchored in objective, mechanism\u2010coupled readouts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70929","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T10:54:12Z","timestamp":1778928852000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Fidelity Paradox in Spinal Cord Injury: Reframing Biomechanical Mimicry and Neurobiological Relevance for Clinical Translation"],"prefix":"10.1002","volume":"32","author":[{"given":"Liang","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Cerebrovascular Diseases The Second Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"},{"name":"Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Traumatic Orthopedics The Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases The Second Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"},{"name":"Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Wee","family":"Yong","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and Department of Clinical Neurosciences University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4427-7285","authenticated-orcid":false,"given":"Mengzhou","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Diseases The Second Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"},{"name":"Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.111675"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.115242"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003306"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70066"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.05.417"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06611-2"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103469"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.373674"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.08.060"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-013-1361-8"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2016.4513"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0114-0"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00282"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10736"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00436-x"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2020.0267"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2021.0194"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00287-9"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.18"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30138-3"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2022.0281"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51855"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2023.102702"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.344839"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.355762"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1992.9.123"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2022.0034"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.72713"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49199"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6731"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102767"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02690-4"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110853"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20827"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00011-0"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.720938"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0576-3"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0509-3"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11203304"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114185"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000003229"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt209"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-112"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.2076"},{"key":"e_1_2_13_46_1","first-page":"1435","article-title":"Percutaneous Translumbar Spinal Cord Compression Injury in Dogs From an Angioplasty Balloon: MR and Histopathologic Changes With Balloon Sizes and Compression Times","volume":"25","author":"Purdy P. 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